rna precursors

Summary

Summary: RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.

Top Publications

  1. ncbi The nuclear RNase III Drosha initiates microRNA processing
    Yoontae Lee
    Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, Seoul 151 742, Korea
    Nature 425:415-9. 2003
  2. pmc Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
    Rui Yi
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Genes Dev 17:3011-6. 2003
  3. ncbi Nuclear export of microRNA precursors
    Elsebet Lund
    Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA
    Science 303:95-8. 2004
  4. ncbi A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA
    G Hutvagner
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Science 293:834-8. 2001
  5. ncbi Identification of novel genes coding for small expressed RNAs
    M Lagos-Quintana
    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, , Germany
    Science 294:853-8. 2001
  6. ncbi Pre-mRNA processing reaches back to transcription and ahead to translation
    Melissa J Moore
    Howard Hughes Medical Institute, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Cell 136:688-700. 2009
  7. pmc The Drosha-DGCR8 complex in primary microRNA processing
    Jinju Han
    School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, 151 742, Korea
    Genes Dev 18:3016-27. 2004
  8. ncbi Human RISC couples microRNA biogenesis and posttranscriptional gene silencing
    Richard I Gregory
    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Cell 123:631-40. 2005
  9. pmc Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
    Mo Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Rev Mol Cell Biol 10:741-54. 2009
  10. ncbi Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex
    Jinju Han
    School of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Seoul
    Cell 125:887-901. 2006

Detail Information

Publications382 found, 100 shown here

  1. ncbi The nuclear RNase III Drosha initiates microRNA processing
    Yoontae Lee
    Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, Seoul 151 742, Korea
    Nature 425:415-9. 2003
    ..Thus, the two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation...
  2. pmc Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
    Rui Yi
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Genes Dev 17:3011-6. 2003
    ..Together, these findings define an additional cellular cofactor required for miRNA biogenesis and function...
  3. ncbi Nuclear export of microRNA precursors
    Elsebet Lund
    Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA
    Science 303:95-8. 2004
    ..Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps...
  4. ncbi A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA
    G Hutvagner
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Science 293:834-8. 2001
    ..Thus, the RNA interference and stRNA pathways intersect. Both pathways require the RNA-processing enzyme Dicer to produce the active small-RNA component that represses gene expression...
  5. ncbi Identification of novel genes coding for small expressed RNAs
    M Lagos-Quintana
    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, , Germany
    Science 294:853-8. 2001
    ..This suggests that sequence-specific, posttranscriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated...
  6. ncbi Pre-mRNA processing reaches back to transcription and ahead to translation
    Melissa J Moore
    Howard Hughes Medical Institute, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Cell 136:688-700. 2009
    ..The connections of pre-mRNA processing to upstream events in transcription and downstream events, including translation and mRNA decay, are elaborate, extensive, and remarkably interwoven...
  7. pmc The Drosha-DGCR8 complex in primary microRNA processing
    Jinju Han
    School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, 151 742, Korea
    Genes Dev 18:3016-27. 2004
    ..Based on these results, we propose a model for the action mechanism of class II RNase III proteins...
  8. ncbi Human RISC couples microRNA biogenesis and posttranscriptional gene silencing
    Richard I Gregory
    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Cell 123:631-40. 2005
    ..Importantly, ATP is not required for miRNA processing, RISC assembly, or multiple rounds of target-RNA cleavage. These results define the composition of RISC and demonstrate that miRNA processing and target-RNA cleavage are coupled...
  9. pmc Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
    Mo Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Rev Mol Cell Biol 10:741-54. 2009
    ..Great progress has been made by studying individual transcripts and through genome-wide approaches, which together provide a better picture of the mechanistic regulation of alternative pre-mRNA splicing...
  10. ncbi Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex
    Jinju Han
    School of Biological Sciences and Research Center for Functional Cellulomics, Seoul National University, Seoul
    Cell 125:887-901. 2006
    ..Our current study thus facilitates the prediction of novel microRNAs and will assist in the rational design of small hairpin RNAs for RNA interference...
  11. ncbi An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans
    N C Lau
    Whitehead Institute for Biomedical Research, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 294:858-62. 2001
    ..The abundance of these tiny RNAs, their expression patterns, and their evolutionary conservation imply that, as a class, miRNAs have broad regulatory functions in animals...
  12. pmc Regulation of alternative splicing by histone modifications
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 327:996-1000. 2010
    ..Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery...
  13. pmc A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity
    Daniel Cifuentes
    Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 328:1694-8. 2010
    ..We propose that Ago2-mediated cleavage of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs independently of Dicer...
  14. pmc Extensive degradation of RNA precursors by the exosome in wild-type cells
    Rajani Kanth Gudipati
    Centre de Genetique Moleculaire, CNRS UPR3404, 91190 Gif sur Yvette, France
    Mol Cell 48:409-21. 2012
    ....
  15. pmc Epigenetics in alternative pre-mRNA splicing
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 144:16-26. 2011
    ..These insights suggest that epigenetic regulation determines not only what parts of the genome are expressed but also how they are spliced...
  16. ncbi Many roads to maturity: microRNA biogenesis pathways and their regulation
    Julia Winter
    Helmholtz University Group Molecular RNA Biology and Cancer, German Cancer Research Center DKFZ and Institute of Pathology, University of Heidelberg, B150 INF 581, D 69120 Heidelberg, Germany
    Nat Cell Biol 11:228-34. 2009
    ..Here we review the recent advances in knowledge of the microRNA biosynthesis pathways and discuss their impact on post-transcriptional microRNA regulation during tumour development...
  17. ncbi The post-transcriptional steps of eukaryotic ribosome biogenesis
    A K Henras
    Laboratoire de Biologie Moleculaire Eucaryote, CNRS, Universite de Toulouse, UPS, 118 route de Narbonne, 31062 Toulouse Cedex 09, France
    Cell Mol Life Sci 65:2334-59. 2008
    ..Moreover, quality control mechanisms are being discovered that monitor ribosome synthesis and degrade the RNA components of defective pre-ribosomal particles...
  18. ncbi Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression
    Sven Diederichs
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Cell 131:1097-108. 2007
    ..The multiple roles of Argonautes in the RNAi effector phase and miRNA biogenesis and maturation suggest coordinate regulation of microRNA expression and function...
  19. ncbi An extensive class of small RNAs in Caenorhabditis elegans
    R C Lee
    Dartmouth Medical School, Department of Genetics, Hanover, NH 03755, USA
    Science 294:862-4. 2001
    ..elegans larval development, and three of them have apparent homologs in mammals and/or insects. Small noncoding RNAs of the miRNA class appear to be numerous and diverse...
  20. ncbi The SR protein family of splicing factors: master regulators of gene expression
    Jennifer C Long
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH42XU, UK
    Biochem J 417:15-27. 2009
    ..Here, we will review the current literature to demonstrate how SR proteins are emerging as one of the master regulators of gene expression...
  21. ncbi Functional siRNAs and miRNAs exhibit strand bias
    Anastasia Khvorova
    Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA
    Cell 115:209-16. 2003
    ..Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC...
  22. pmc Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing
    Robert J Sims
    Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 28:665-76. 2007
    ..These findings suggest that methylated H3K4 serves to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3K4me3 via CHD1...
  23. pmc U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
    Daisuke Kaida
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    Nature 468:664-8. 2010
    ..These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance...
  24. ncbi CLIP identifies Nova-regulated RNA networks in the brain
    Jernej Ule
    Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    Science 302:1212-5. 2003
    ..Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA...
  25. pmc A cluster of ribosome synthesis factors regulate pre-rRNA folding and 5.8S rRNA maturation by the Rat1 exonuclease
    Sander Granneman
    Wellcome Trust Centre for Cell Biology and Centre for Systems Biology at Edinburgh, University of Edinburgh, Edinburgh, Scotland
    EMBO J 30:4006-19. 2011
    ..We predict that Nop4 and the A(3) cluster establish long-range interactions between the 5.8S and 25S rRNAs, which are subsequently maintained by ribosomal protein binding...
  26. pmc Molecular mechanisms of eukaryotic pre-mRNA 3' end processing regulation
    Stefania Millevoi
    Institut National de la Sante et de la Recherche Medicale U563, Toulouse, F 31000, France
    Nucleic Acids Res 38:2757-74. 2010
    ....
  27. pmc Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs
    Markus T Bohnsack
    Zentrum fur Molekulare Biologie, Heidelberg, Germany
    RNA 10:185-91. 2004
    ..We further show that exportin 5 interacts with double-stranded RNA in a sequence-independent manner...
  28. pmc ESEfinder: A web resource to identify exonic splicing enhancers
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Nucleic Acids Res 31:3568-71. 2003
    ....
  29. ncbi CLIP: a method for identifying protein-RNA interaction sites in living cells
    Jernej Ule
    Howard Hughes Medical Institute and the Laboratory of Molecular Neuro Oncology, The Rockefeller University, New York, USA
    Methods 37:376-86. 2005
    ..Here, we present an improved protocol that performs RNA linker ligation before the SDS-PAGE step, and describe its application to the specific purification and amplification of RNA ligands of Nova in neurons...
  30. pmc Intronic microRNA precursors that bypass Drosha processing
    J Graham Ruby
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 448:83-6. 2007
    ..This suggests that other lineages with many similarly sized introns probably also have mirtrons, and that the mirtron pathway could have provided an early avenue for the emergence of miRNAs before the advent of Drosha...
  31. pmc Molecular architecture of the human pre-mRNA 3' processing complex
    Yongsheng Shi
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Mol Cell 33:365-76. 2009
    ..Together, our data has revealed the complexity and molecular architecture of the pre-mRNA 3' processing complex...
  32. ncbi The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a
    Sonia Guil
    Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK
    Nat Struct Mol Biol 14:591-6. 2007
    ..These results underscore a previously uncharacterized role for general RNA-binding proteins as auxiliary factors that facilitate the processing of specific miRNAs...
  33. pmc Yeast pre-rRNA processing and modification occur cotranscriptionally
    Martin Kos
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK
    Mol Cell 37:809-20. 2010
    ..8S rRNAs was partially methylated on the nascent transcript. The results demonstrate that quantitative analyses of pre-rRNA processing can yield important biological insights...
  34. pmc Identification of protein binding sites on U3 snoRNA and pre-rRNA by UV cross-linking and high-throughput analysis of cDNAs
    Sander Granneman
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, Scotland
    Proc Natl Acad Sci U S A 106:9613-8. 2009
    ..This finding demonstrates that the snoRNP proteins directly contact the pre-rRNA substrate, suggesting roles in snoRNA recruitment. The techniques reported here should be widely applicable to analyses of RNA-protein interactions...
  35. pmc Frequency and fate of microRNA editing in human brain
    Yukio Kawahara
    The Wistar Institute
    Nucleic Acids Res 36:5270-80. 2008
    ..Our studies predict that approximately 16% of human pri-miRNAs are subject to A-->I editing and, thus, miRNA editing could have a large impact on the miRNA-mediated gene silencing...
  36. pmc Hierarchical rules for Argonaute loading in Drosophila
    Benjamin Czech
    Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Mol Cell 36:445-56. 2009
    ....
  37. pmc Role of RNA structure in regulating pre-mRNA splicing
    M Bryan Warf
    Institute of Molecular Biology, and Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA
    Trends Biochem Sci 35:169-78. 2010
    ..Recent reports have identified proteins and small molecules that can regulate splicing by modulating RNA structures, thereby expanding our knowledge of the mechanisms used to regulate splicing...
  38. ncbi Global analysis of nascent RNA reveals transcriptional pausing in terminal exons
    Fernando Carrillo Oesterreich
    Max Planck Institute of Molecular Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Mol Cell 40:571-81. 2010
    ..The discovery of terminal exon pausing demonstrates functional coupling of transcription and splicing near gene ends...
  39. pmc Pre-mRNA splicing is a determinant of histone H3K36 methylation
    Soojin Kim
    Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    Proc Natl Acad Sci U S A 108:13564-9. 2011
    ..These results suggest that the cotranscriptional splicing apparatus influences establishment of normal patterns of histone modification...
  40. pmc Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs
    Xuezhong Cai
    Box 3025, Duke University Medical Center, Durham, NC 27710, USA
    RNA 10:1957-66. 2004
    ..Together, these data show that human pri-miRNAs are not only structurally similar to mRNAs but can, in fact, function both as pri-miRNAs and mRNAs...
  41. pmc Structural basis of microRNA length variety
    Julia Starega-Roslan
    Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego, Poznan, Poland
    Nucleic Acids Res 39:257-68. 2011
    ..The relevance of these findings to the dynamics of the dicing complex, mRNA regulation by miRNA, RNA interference and miRNA technologies are discussed...
  42. ncbi Genome-wide analyses of alternative splicing in plants: opportunities and challenges
    W Brad Barbazuk
    Donald Danforth Plant Science Center, St Louis, Missouri 63132, USA
    Genome Res 18:1381-92. 2008
    ..This review summarizes recent analyses of AS in plants, discusses the importance of further analysis, and suggests directions for future efforts...
  43. ncbi microPred: effective classification of pre-miRNAs for human miRNA gene prediction
    Rukshan Batuwita
    Oxford University Computing Laboratory, University of Oxford, Wolfson Building, Oxford, UK
    Bioinformatics 25:989-95. 2009
    ....
  44. pmc Dual roles of the nuclear cap-binding complex and SERRATE in pre-mRNA splicing and microRNA processing in Arabidopsis thaliana
    Sascha Laubinger
    Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany
    Proc Natl Acad Sci U S A 105:8795-800. 2008
    ..Taken together, our results uncover dual roles in splicing and miRNA processing that distinguish SE and the cap-binding complex from specialized miRNA processing factors such as DCL1 and HYL1...
  45. pmc RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex
    Yukio Kawahara
    The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    EMBO Rep 8:763-9. 2007
    ....
  46. ncbi Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA
    Daisuke Kaida
    Chemical Genetics Laboratory, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Nat Chem Biol 3:576-83. 2007
    ..Thus, the inhibition of pre-mRNA splicing during early steps involving SF3b allows unspliced mRNA leakage and translation...
  47. pmc A link between nuclear RNA surveillance, the human exosome and RNA polymerase II transcriptional termination
    Sérgio F de Almeida
    Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649 028 Lisboa, Portugal
    Nucleic Acids Res 38:8015-26. 2010
    ..This reveals an unprecedented link between nuclear RNA surveillance, the exosome and Pol II transcriptional termination...
  48. pmc The in vivo kinetics of RNA polymerase II elongation during co-transcriptional splicing
    Yehuda Brody
    The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar Ilan University, Ramat Gan, Israel
    PLoS Biol 9:e1000573. 2011
    ..This suggests that the polymerase is released from chromatin prior to the completion of splicing, and the pre-mRNA is post-transcriptionally processed while still tethered to chromatin near the gene end...
  49. ncbi Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs
    M E Nemeroff
    Department of Molecular Biology and Biochemistry Rutgers University Piscataway, New Jersey 08854, USA
    Mol Cell 1:991-1000. 1998
    ..Via this novel regulation of pre-mRNA 3' end processing, the NS1 protein selectively inhibits the nuclear export of cellular, and not viral, mRNAs...
  50. ncbi Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA
    Inha Heo
    National Creative Research Center and School of Biological Sciences, Seoul National University, Seoul 151 742, Korea
    Mol Cell 32:276-84. 2008
    ..The Lin28-mediated downregulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis...
  51. ncbi SR proteins function in coupling RNAP II transcription to pre-mRNA splicing
    Rita Das
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 26:867-81. 2007
    ..Thus, these factors readily out-compete inhibitory hnRNP proteins, resulting in efficient spliceosome assembly on nascent RNAP II transcripts...
  52. ncbi MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation
    Hiroshi I Suzuki
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Mol Cell 44:424-36. 2011
    ..The presence of this abortive processing machinery and diversity of MCPIP1-related genes may imply a dynamic evolutional transition of the RNA silencing system...
  53. pmc Muscleblind-like 1 interacts with RNA hairpins in splicing target and pathogenic RNAs
    Yuan Yuan
    Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL, USA
    Nucleic Acids Res 35:5474-86. 2007
    ..Our results provide a mechanistic basis for dsCUG-induced MBNL1 sequestration and highlight a striking similarity in the binding sites for MBNL proteins on splicing precursor and pathogenic RNAs...
  54. ncbi Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA
    Ranhui Duan
    Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hum Mol Genet 16:1124-31. 2007
    ..Thus, our study reveals an additional structural requirement for pri-miRNA processing and emphasizes the importance of identifying new miRNA SNPs and their contributions to miRNA biogenesis and human genetic disease...
  55. pmc Functional integration of transcriptional and RNA processing machineries
    Shatakshi Pandit
    Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0651, United States
    Curr Opin Cell Biol 20:260-5. 2008
    ....
  56. pmc RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes
    Kira Glover-Cutter
    Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, UCHSC, MS8101, PO Box 6511, Aurora, Colorado 80045, USA
    Nat Struct Mol Biol 15:71-8. 2008
    ..We propose a dual-pausing model wherein elongation arrests near the transcription start site and in the 3' flank to allow co-transcriptional processing by factors recruited to the pol II ternary complex...
  57. pmc The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay
    H Le Hir
    Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    EMBO J 20:4987-97. 2001
    ..Finally, we show that the composition of the EJC is dynamic in vivo and is subject to significant evolution upon mRNA export to the cytoplasm...
  58. ncbi Pre-18S ribosomal RNA is structurally compacted into the SSU processome prior to being cleaved from nascent transcripts in Saccharomyces cerevisiae
    Yvonne N Osheim
    Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA
    Mol Cell 16:943-54. 2004
    ..The results show that the approximately 40 components of the SSU processome/90S preribosome can complete their tasks within approximately 85 s in optimal conditions...
  59. pmc Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer
    Krystian Jazdzewski
    Human Cancer Genetics Program, Comprehensive Cancer Center and Division of Endocrinology, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 106:1502-5. 2009
    ..Heterozygosity for polymorphisms within the premiR sequence can cause epistasis through the production of additional mature miRs. We propose that mature miRs from the passenger strand may regulate many genetic processes...
  60. pmc Splicing regulation: from a parts list of regulatory elements to an integrated splicing code
    Zefeng Wang
    Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    RNA 14:802-13. 2008
    ..Here, we summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions...
  61. pmc The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3' processing and transcription termination
    Syuzo Kaneko
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Genes Dev 21:1779-89. 2007
    ..Together, our data indicate that p54nrb/PSF functions in recruitment of XRN2 to facilitate pre-mRNA 3' processing and transcription termination...
  62. pmc The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila
    Katsutomo Okamura
    Memorial Sloan Kettering Cancer Center, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10021, USA
    Cell 130:89-100. 2007
    ..These findings reveal that mirtrons are an alternate source of miRNA-type regulatory RNAs...
  63. ncbi Identification of a regulated pathway for nuclear pre-mRNA turnover
    C Bousquet-Antonelli
    Wellcome Trust Centre for Cell Biology ICMB, University of Edinburgh, Scotland
    Cell 102:765-75. 2000
    ..We propose that nuclear pre-mRNA turnover represents a novel step in the regulation of gene expression...
  64. pmc Deep sequencing reveals differential expression of microRNAs in favorable versus unfavorable neuroblastoma
    Johannes H Schulte
    University Children s Hospital Essen, Hufelandstr 55, 45122 Essen, Germany
    Nucleic Acids Res 38:5919-28. 2010
    ..In-depth sequence analysis revealed extensive post-transcriptional miRNA editing. Of 13 identified novel miRNAs, three were further analyzed, and expression could be confirmed in a cohort of 70 NBs...
  65. ncbi Alternative splicing of pre-mRNAs of Arabidopsis serine/arginine-rich proteins: regulation by hormones and stresses
    Saiprasad Goud Palusa
    Department of Biology, Colorado State University, Fort Collins, CO 80523, USA
    Plant J 49:1091-107. 2007
    ..Together our results indicate that Arabidopsis SR genes generate surprisingly large transcriptome complexity, which is altered by stresses and hormones...
  66. pmc RNA helicase Prp43 and its co-factor Pfa1 promote 20 to 18 S rRNA processing catalyzed by the endonuclease Nob1
    Brigitte Pertschy
    Biochemie Zentrum der Universitat Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
    J Biol Chem 284:35079-91. 2009
    ..In ltv1/pfa1 mutants the 20 S pre-rRNA was susceptible to 3' to 5' degradation by the cytoplasmic exosome. This degraded into the 3' region of the 18 S rRNA, strongly indicating that the preribosomes are structurally defective...
  67. pmc Ribosomal proteins L7 and L8 function in concert with six A₃ assembly factors to propagate assembly of domains I and II of 25S rRNA in yeast 60S ribosomal subunits
    Jelena Jakovljevic
    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA
    RNA 18:1805-22. 2012
    ..Thus, L7 and L8 might establish RNP structures within assembling ribosomes necessary for the stable association and function of the A(3) assembly factors and for proper assembly of the neighborhoods containing domains I and II...
  68. pmc Hierarchical recruitment into nascent ribosomes of assembly factors required for 27SB pre-rRNA processing in Saccharomyces cerevisiae
    Jason Talkish
    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA
    Nucleic Acids Res 40:8646-61. 2012
    ..Inhibition of TOR kinase decreases association of Rpf2, Spb4, Nog1 and Nog2 with pre-ribosomes...
  69. pmc Deep sequencing of microRNA precursors reveals extensive 3' end modification
    Martin A Newman
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    RNA 17:1795-803. 2011
    ..This work provides an unprecedented view of the complexity of 3' modification and trimming of miRNA precursors...
  70. ncbi A Pre-mRNA degradation pathway that selectively targets intron-containing genes requires the nuclear poly(A)-binding protein
    Caroline Lemieux
    RNA Group, Department of Biochemistry, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
    Mol Cell 44:108-19. 2011
    ..Our findings unveil a layer of regulation in the nucleus in which the turnover of specific pre-mRNAs, besides the turnover of mature mRNAs, is used to control gene expression...
  71. pmc Assembly of Saccharomyces cerevisiae 60S ribosomal subunits: role of factors required for 27S pre-rRNA processing
    Aarti Sahasranaman
    Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA
    EMBO J 30:4020-32. 2011
    ..In the absence of these assembly factors, at least one exonuclease can switch from processing to turnover of pre-rRNA...
  72. pmc Promotion of exon 6 inclusion in HuD pre-mRNA by Hu protein family members
    Huiwen Wang
    Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA
    Nucleic Acids Res 38:3760-70. 2010
    ..Our studies demonstrate that Hu proteins can function as splicing enhancers and expand the functional role of Hu proteins as splicing regulators...
  73. pmc An RNA conformational switch regulates pre-18S rRNA cleavage
    Allison C Lamanna
    Department of Chemistry, University of Michigan, Ann Arbor, MI 48109 1055, USA
    J Mol Biol 405:3-17. 2011
    ..More generally, our data show that the intrinsic ability of RNA to form stable structural switches is exploited to order and regulate RNA-dependent biological processes...
  74. pmc The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove
    Richard Stefl
    Institute of Molecular Biology and Biophysics, ETH Zurich, CH 8093 Zurich, Switzerland
    Cell 143:225-37. 2010
    ..More generally, our findings suggest a solution to the sequence-specific paradox faced by many dsRBM-containing proteins that are involved in post-transcriptional regulation of gene expression...
  75. pmc Mammalian mirtron genes
    Eugene Berezikov
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell 28:328-36. 2007
    ..This notion is supported by our observation of several clade-specific features of mammalian and invertebrate mirtrons...
  76. pmc Protein factors in pre-mRNA 3'-end processing
    C R Mandel
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Cell Mol Life Sci 65:1099-122. 2008
    ..The yeast machinery includes cleavage factor IA, cleavage factor IB, and cleavage and polyadenylation factor...
  77. pmc Human miRNA precursors with box H/ACA snoRNA features
    Michelle S Scott
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, United Kingdom
    PLoS Comput Biol 5:e1000507. 2009
    ..The detection of small RNA molecules that share features of miRNAs and snoRNAs suggest that these classes of RNA may have an evolutionary relationship...
  78. ncbi 90S pre-ribosomes include the 35S pre-rRNA, the U3 snoRNP, and 40S subunit processing factors but predominantly lack 60S synthesis factors
    Paola Grandi
    Cellzome AG, Meyerhofstrasse 1, 69117, Heidelberg, Germany
    Mol Cell 10:105-15. 2002
    ..We conclude that the 40S synthesis machinery predominately associates with the 35S pre-rRNA factors, whereas factors required for 60S subunit synthesis largely bind later, showing an unexpected dichotomy in binding...
  79. pmc The final step in 5.8S rRNA processing is cytoplasmic in Saccharomyces cerevisiae
    Emma Thomson
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, Scotland, UK
    Mol Cell Biol 30:976-84. 2010
    ..We conclude that nuclear pre-60S particles containing the 6S pre-rRNA bind Nmd3 and Crm1 and are exported to the cytoplasm prior to final maturation by Ngl2...
  80. pmc Expanded RNA-binding activities of mammalian Argonaute 2
    Grace S Tan
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Nucleic Acids Res 37:7533-45. 2009
    ..Furthermore, we demonstrate that, in vivo, endogenous human Ago2 binds directly to pre-miRNAs independently of Dicer, and that Ago2:pre-miRNA complexes are found both in the cytoplasm and in the nucleus of human cells...
  81. ncbi Exon identity established through differential antagonism between exonic splicing silencer-bound hnRNP A1 and enhancer-bound SR proteins
    J Zhu
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Mol Cell 8:1351-61. 2001
    ..The differential antagonism between a negative and two positive regulators exemplifies how inclusion of an alternative exon can be modulated...
  82. ncbi Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing
    Nicolas Charlet-B
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell 10:45-53. 2002
    ..We propose that disruption of alternative splicing regulation causes a predominant pathological feature of DM1...
  83. ncbi An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers
    Philip J Smith
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Hum Mol Genet 15:2490-508. 2006
    ..Finally, we have derived an increased specificity score matrix that incorporates information from both of our SF2/ASF-specific matrices and that accurately predicts the exon-skipping phenotypes of deleterious point mutations...
  84. ncbi Mechanisms of alternative pre-messenger RNA splicing
    Douglas L Black
    Department of Microbiology, Immunology, and Molecular Genetics, Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, California 90095 1662, USA
    Annu Rev Biochem 72:291-336. 2003
    ..How these regulators are combined into complex systems of tissue-specific splicing is discussed. In conclusion, very recent studies are presented that point to new directions for understanding alternative splicing and its mechanisms...
  85. ncbi The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data
    Marc Parisien
    Institute for Research in Immunology and Cancer, Department of Computer Science and Operations Research, Universite de Montreal, PO Box 6128, Downtown Station, Montreal, Quebec H3C 3J7, Canada
    Nature 452:51-5. 2008
    ....
  86. ncbi RNA maps reveal new RNA classes and a possible function for pervasive transcription
    Philipp Kapranov
    Affymetrix Laboratory, Affymetrix, Inc, 3420 Central Expressway, Santa Clara, CA, 95051, USA
    Science 316:1484-8. 2007
    ..These data support a highly interleaved organization of the human transcriptome...
  87. pmc Prp5 bridges U1 and U2 snRNPs and enables stable U2 snRNP association with intron RNA
    Yong Zhen Xu
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA
    EMBO J 23:376-85. 2004
    ..pombe. Together, these data are consistent with Prp5 being a bridge between U1 and U2 snRNPs at the time of pre-spliceosome formation...
  88. pmc A LIN28-dependent structural change in pre-let-7g directly inhibits dicer processing
    Helen L Lightfoot
    Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK
    Biochemistry 50:7514-21. 2011
    ..The data support a mechanism by which LIN28 can directly inhibit let-7g biogenesis at the Dicer processing step...
  89. pmc pre-miRNA profiles obtained through application of locked nucleic acids and deep sequencing reveals complex 5'/3' arm variation including concomitant cleavage and polyuridylation patterns
    A Maxwell Burroughs
    Omics Science Center, RIKEN Yokohama Institute, 1 7 22 Suehiro cho, Tsurumi ku, Yokohama shi, Kanagawa 230 0045, Japan
    Nucleic Acids Res 40:1424-37. 2012
    ....
  90. ncbi hnRNP A1 proofreads 3' splice site recognition by U2AF
    João Paulo Tavanez
    Centre de Regulacio Genomica, Dr Aiguader 88, 08003 Barcelona, Spain Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain
    Mol Cell 45:314-29. 2012
    ..Consistent with the functional relevance of this activity for splicing, proofreading assays reveal a role for hnRNP A1 in U2AF-mediated recruitment of U2 snRNP to the pre-mRNA...
  91. ncbi Structural basis for recognition of the intron branch site RNA by splicing factor 1
    Z Liu
    European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Science 294:1098-102. 2001
    ..The branch point adenosine acting as the nucleophile in the first biochemical step of splicing is deeply buried. BPS RNA recognition suggests how SF1 may facilitate subsequent formation of the prespliceosomal complex A...
  92. pmc A role for c-Myc in the regulation of ribosomal RNA processing
    Isabel Schlosser
    GSF National Research Centre for Environment and Health, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, 81377 Munich, Germany
    Nucleic Acids Res 31:6148-56. 2003
    ..As processing of rRNA is sensitive to inhibition of cyclin-dependent kinase (cdk) activity by roscovitine, we conclude that c-Myc regulates cell growth and proliferation by the coordinated induction of cdk activity and rRNA processing...
  93. pmc 5'-end surveillance by Xrn2 acts as a shared mechanism for mammalian pre-rRNA maturation and decay
    Minshi Wang
    Department of Cell Biology, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA
    Nucleic Acids Res 39:1811-22. 2011
    ..We propose that probing of pre-rRNA maturation intermediates by exonucleases serves the dual function of generating mature rRNAs and suppressing suboptimal processing paths during ribosome assembly...
  94. ncbi Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy
    Ami Mankodi
    Department of Neurology, School of Medicine and Dentistry, University of Rochester, Box 673, 601 Elmwood Avenue, New York 14642, USA
    Mol Cell 10:35-44. 2002
    ..We propose that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM...
  95. pmc Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits
    Marie Françoise O'Donohue
    Laboratoire de Biologie Moléculaire des Eucaryotes, Université de Toulouse UPS and Centre National de La Recherche Scientifique, F 31000 Toulouse, France
    J Cell Biol 190:853-66. 2010
    ..Interestingly, the functional dichotomy of RPS proteins reported in this study is correlated with the mutation frequency of RPS genes in Diamond-Blackfan anemia...
  96. ncbi Splicing segregation: the minor spliceosome acts outside the nucleus and controls cell proliferation
    Harald König
    Forschungszentrum Karlsruhe GmbH, Institut für Toxikologie und Genetik, Postfach 3640, 76021 Karlsruhe, Germany
    Cell 131:718-29. 2007
    ..The segregation offers a mechanism accounting for spliceosome evolution in a single lineage and provides a means for nucleus-independent control of gene expression...
  97. pmc Rational extension of the ribosome biogenesis pathway using network-guided genetics
    Zhihua Li
    Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas, USA
    PLoS Biol 7:e1000213. 2009
    ....
  98. pmc Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription
    Shouhong Guang
    Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA
    Nature 465:1097-101. 2010
    ..In addition, these results establish a novel mode of RNAP II regulation: siRNA-directed recruitment of NRDE factors that inhibit RNAP II during the elongation phase of transcription...
  99. pmc Conservation of the protein composition and electron microscopy structure of Drosophila melanogaster and human spliceosomal complexes
    Nadine Herold
    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany
    Mol Cell Biol 29:281-301. 2009
    ..These studies provide insights into the evolutionarily conserved composition and structure of the metazoan spliceosome, as well as its compositional dynamics during catalytic activation...
  100. pmc Modulation of RNA editing by functional nucleolar sequestration of ADAR2
    Christopher L Sansam
    Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 100:14018-23. 2003
    ..These observations indicate that the nucleolar localization of ADAR2 represents an important mechanism by which RNA editing can be modulated by the sequestration of enzymatic activity from potential RNA substrates in the nucleoplasm...
  101. pmc Gene structures and processing of Arabidopsis thaliana HYL1-dependent pri-miRNAs
    Bogna Szarzynska
    Department of Gene Expression, Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland
    Nucleic Acids Res 37:3083-93. 2009
    ..In the hyl1 mutant intron-containing pri-miRNAs accumulate alongside spliced pri-miRNAs suggesting the recruitment of HYL1 into the miRNA precursor maturation pathway before their splicing occurs...

Research Grants74

  1. Lung Lysyl Oxidase Regulation by Metal Ion Homeostasis
    Wande Li; Fiscal Year: 2013
    ..The outcomes of the proposed research are expected to enhance our understanding of mechanisms of LO gene silence by Cd providing the basis for developing prophylaxis and treatment strategies for Cd-related lung diseases. ..
  2. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..The proposed studies are aimed at understanding basic cellular mechanisms of gene expression, and may provide the basis for developing or improving diagnostic tools and therapeutic agents for these diseases. ..
  3. Molecular Mechanisms of Parvovirus Gene Expression and Replication
    Jianming Qiu; Fiscal Year: 2013
    ..e., EPCs ex vivo-expanded under hypoxic conditions for B19V in this application. ..
  4. ANALYSIS OF TRYPANOSOME MRNA SYNTHESIS BY GENE TRANSFER
    Vivian Bellofatto; Fiscal Year: 2010
    ..The goal of our biomedical work is to define unique features of trypanosome biology and then to exploit these traits for the design of anti-parasitic chemotherapies. ..
  5. High-affinity RNA targets of Survival Motor Neuron Protein
    Ravindra N Singh; Fiscal Year: 2013
    ..Our proposal has potential to identify novel SMN functions with significance to a better understanding of molecular mechanism of SMA pathogenesis. ) ..
  6. The molecular mechanism of Aire: partnering with DNA-PK
    Diane J Mathis; Fiscal Year: 2013
    ..Targeting certain of the new molecular interactions and pathways highlighted in this study may have therapeutic potential. ..
  7. Functional characterization of the Bronx waltzer deafness gene
    Botond Banfi; Fiscal Year: 2013
    ....
  8. The Role of RNA Splicing Factors in Retinal Degeneration
    Michael Farkas; Fiscal Year: 2012
    ..We believe that if we can identify the specific splicing alterations that cause RP in patients with these disorders, it is possible that similar therapeutic approaches could be developed for treating these diseases. ..
  9. ANALYSIS OF NEMATODE SEX DETERMINATION
    Barbara J Meyer; Fiscal Year: 2013
    ..Our protein complexes give us insight into the mechanisms underlying the genome rearrangements associated with such a cancerous state. ..
  10. Noncoding RNA targets of the spinal muscular atrophy protein
    Livio Pellizzoni; Fiscal Year: 2010
    ..These studies have the potential to provide unanticipated insights into the molecular mechanisms of SMA and to suggest new avenues of therapeutic intervention. ..
  11. Structural Studies of RNA Maturation and Processing
    Christopher D Lima; Fiscal Year: 2013
    ..Pathways and enzymes that regulate the abundance, lifetime, and processing of RNA have been associated with human diseases that include neurodegenerative disorders, cancer, and inflammation. ..
  12. SPLICING OF MRNA PRECURSORS
    Michael R Green; Fiscal Year: 2013
    ....
  13. RNA polymerase II transcription in trypanosomes
    ARTHUR GUNZL; Fiscal Year: 2013
    ..Moreover, a thorough understanding of trypanosome gene expression will help to control the parasite in the long term. ..
  14. Small Oligonucleotides As Therapeutic Agents Of Spinal Muscular Atrophy
    Ravindra N Singh; Fiscal Year: 2012
    ..The success of this proposal will provide a mechanism-based and target- specific drug for the treatment of SMA. ) ..
  15. Expression control in Drosophila splicing assembly factor RNP-4F
    JACK VAUGHN; Fiscal Year: 2010
    ..In this proposal, we outline experiments which are designed to result in understanding the roles of cis- and trans-acting regulatory factors in genetic regulation of this evolutionarily-conserved splicing assembly factor. ..
  16. The Role of a New Cleavage and Polyadenylation Specificity Factor (CPSF73-II)
    Qingshun Q Li; Fiscal Year: 2010
    ..The latter is known to be relevant to many human health and disease control issues. ..
  17. Mechanism Underlying Neurodegeneration Caused by Dysfunction of Pre-mRNA Splicing
    Yichang Jia; Fiscal Year: 2012
    ..The potential outcome from the experiments outlined in this proposal will not only help us better understand the disease mechanisms of these diseases but will also provide a basis for the development of rational therapeutic strategies. ..
  18. Mechanisms of Gene Regulation by EBV EBNA-1 Protein
    Jeffery T Sample; Fiscal Year: 2010
    ....
  19. Defining the messenger RNP code in the brain
    EUGENE WEI MING YEO; Fiscal Year: 2013
    ..Finally, we will leverage our computational expertise to build predictive models using this genome-wide, multi-scale, mRNP code in the brain. ..
  20. Mechanisms of Src activation and its role in latent bone metastasis of breast and
    Xiang H F Zhang; Fiscal Year: 2010
    ..Because of the availability of FDA-approved Src inhibitors, this study will carry significant clinical implications and may suggest novel therapeutic strategies that can be immediately subject to clinical trials. ..
  21. Alternative Splicing in Regulation of Cholesterol Synthesis and Uptake
    Marisa Wong Medina; Fiscal Year: 2013
    ....
  22. Coupling of Transcription with Pre-mRNA Metabolism
    DAVID LEONARD BENTLEY; Fiscal Year: 2013
    ..This study will help identify defects in the function of the 'mRNA factory" that may play a major role in corrupting splicing and cleavage/polyadenylation in cancer cells. ..
  23. Specification of alternate siRNA biogenesis pathways in Arabidopsis
    TODD LUCAS BLEVINS; Fiscal Year: 2011
    ..assays will test whether each RDR or DCL-interacting protein is functionally required for conversion of RNA precursors to products in either siRNA biogenesis pathway...
  24. The Role of Caspase 9b Expression in NSCLC Survival/Chemotherapeutic Sensitivity
    Charles E Chalfant; Fiscal Year: 2013
    ..g. cisplatinum and paclitaxel). ..
  25. Regulation of caspase 9 RNA splicing in NSCLC cancer
    Charles E Chalfant; Fiscal Year: 2013
    ....
  26. Enzymology of RNA Processing
    Carol A Fierke; Fiscal Year: 2013
    ....
  27. PHOSPHOINOSITIDE SIGNALING TO AND WITHIN THE NUCLEUS
    Richard A Anderson; Fiscal Year: 2012
    ..The regulation of pre-mRNA polyadenylation by phosphoinositide signals via PIPKI[unreadable] and Star-PAP is an incredibly novel finding that has many implications for nuclear signal transduction and gene expression. ..
  28. Macronutrient Regulation of Alternative Pre-mRNA Splicing
    Scot R Kimball; Fiscal Year: 2013
    ....
  29. Monoallelic repair of expanded huntingtin by trans-splicing
    Hansjorg Rindt; Fiscal Year: 2011
    ..An inherited mutation causes the death of neurons in the brain. This project explores the possibility of repairing the mutation and to restore normal cellular functions. ..
  30. mRNA Capping Enzymes
    STEWART H SHUMAN; Fiscal Year: 2013
    ..In this project, we propose to dissect genetically and biochemically the phosphoprotein substrate specificity of S. pombe Fcp1 and the requirements for Fcp1 function in vivo. ..
  31. Roles of MLL histone methyalses in estrogen mediated regulation of HDLR-SRB1
    Subhrangsu Mandal; Fiscal Year: 2010
    ..Completion of these studies will advance our understanding about CVD and cancer and will open up new avenues for potential therapy. 1 ..
  32. Spliceosome Mechanism Dissected at the Single Molecule Level
    Nils G Walter; Fiscal Year: 2013
    ..Taken together, these advances will pave the way for, over the funding period, extensive mechanistic studies of yeast splicing and for studying alternative splicing in humans in the longer term. ..
  33. Functional Coupling of Steps in Genes Expression
    ROBIN E REED; Fiscal Year: 2013
    ..Important insights into the essential cellular process of mRNA export is anticipated from these studies. ..
  34. MECHANISMS OF ENHANCER DEPENDENT SPLICE SITE ACTIVATION
    Klemens J Hertel; Fiscal Year: 2013
    ....
  35. Amino Acid Regulation of Alternative Splicing
    Michael S Kilberg; Fiscal Year: 2013
    ..The insight gained from these studies will impact the fields of: 1) macro-nutrient control of pre- mRNA alternative splicing;2) amino acid-dependent control of transcription;and 3) ATF3 function in nutrition and disease. ..
  36. MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY
    THOMAS ALEXANDER COOPER; Fiscal Year: 2013
    ..These results will provide new therapeutic targets to prevent or circumvent the molecular events leading to muscle wasting. ..
  37. TORC2-dependent regulation of gluconeogensis
    MICHAEL DALE CONKRIGHT; Fiscal Year: 2012
    ..By studying the mechanisms of regulation of key gluconeogenic genes we will uncover key therapeutic targets. ..
  38. New Models to Assay Gene Silencing Therapies
    Ronald J Mandel; Fiscal Year: 2012
    ....
  39. Recognition of Regulatory and Pathogenic RNA by Muscleblind Zinc Fingers
    PETER EDWIN WRIGHT; Fiscal Year: 2010
    ....
  40. Nuclear Export of Retroviral RNPs: Cytoplasmic fates determined in the nucleus
    REBECCA J KADDIS; Fiscal Year: 2013
    ....
  41. Development of RIP-Chip methods and tiled arrays to identify functional elements
    Michael L Whitfield; Fiscal Year: 2010
    ..Understanding the regulatory code that directs the expression of genes at all levels (transcription, pre-mRNA processing, translational control and RNA stability) will provide a better understanding of this basic process. ..
  42. The role of the SF3B1 splicing factor in chronic lymphocytic leukemia
    CATHERINE JU YING WU; Fiscal Year: 2013
    ....
  43. MECHANISMS FOR REARRANGING RNA DURING PRE-MRNA SPLICING
    Jonathan P Staley; Fiscal Year: 2013
    ..A major goal of our work is to determine how errors in this process are prevented to better understand the etiology of disease and how to treat disease. ..
  44. Transcriptional elongation and splicing in human genes in situ
    Richard A Padgett; Fiscal Year: 2013
    ..These studies will advance our understanding of human gene expression which is of major relevance to both normal and pathological cell growth and development. ..
  45. SMA mouse models: splicing manipulation and therapeutic SMN replacement
    CATHERINE DOMINGUEZ; Fiscal Year: 2013
    ....
  46. Human DBR1 defines a new pathway of intrinsic antiviral immunity in the CNS
    Shen Ying Zhang; Fiscal Year: 2013
    ..This research will shed light on a novel molecule and cellular mechanism of the HSE pathogenesis, which will open new therapeutic avenues. ..
  47. Viral and Microbial RNA Modifying Enzymes
    STEWART H SHUMAN; Fiscal Year: 2013
    ....
  48. Regulation of Exercise-Induced IL-6 Expression in Skeletal Muscle
    David L Allen; Fiscal Year: 2010
    ....
  49. Regulation of Substrate Binding and Catalysis in tRNase Z
    LOUIS F LEVINGER; Fiscal Year: 2010
    ..Additionally, the gene that encodes tRNase ZL (Elac2, one of the enzymes in the tRNA maturation pathway) has been associated with an elevated risk of prostate cancer, making the proposed research biomedically relevant. ..
  50. Tetracycline derivatives as SMN2 mRNA splicing modifiers for treatment of SMA.
    S Ken Tanaka; Fiscal Year: 2013
    ..The drug is intended to prolong and improve the quality of life for children and adults with SMA, a disease for which there presently is no cure. ..
  51. Trans-splicing in C. elegans
    Thomas Blumenthal; Fiscal Year: 2011
    ....
  52. MECHANISM OF PRE-MRNA SPLICING
    MAGDA KONARSKA; Fiscal Year: 2012
    ..The proposed studies, aimed at understanding the function of the yeast spliceosome, are expected to explain some fundamental properties of alternative splicing in human cells. ..
  53. Protocadherin Gene Expression and Function
    THOMAS P MANIATIS; Fiscal Year: 2012
    ..Taken together, these studies should provide significant new insights into the generation and function of single cell diversity i the brain. ..
  54. Hu proteins as novel splicing regulators in neurons
    Hua Lou; Fiscal Year: 2013
    ..The CNS neuronal differentiation system to be developed will serve as a valuable new alternative model in studies of neuron-specific splicing regulation. ..
  55. The Regulation of PP1 in the Nucleus
    Rebecca Page; Fiscal Year: 2013
    ..Furthermore, it has the preliminary data that demonstrates that this work will provide unique, novel insights into the molecular regulation of PP1. ..
  56. Structural studies of RNase P
    ALFONSO MONDRAGON; Fiscal Year: 2013
    ..RNase P is a promising target for the development of new chemotherapeutics as the specificity of RNase P can be altered to create molecules that degrade target RNA molecules. ..
  57. REGULATION OF GENE EXPRESSION IN CARTILAGE
    Linda Sandell; Fiscal Year: 2009
    ..Regulatory factors will be tested by over expression and inhibition studies and correlated with expression in vivo. ..
  58. Functional Analysis of CDKp110 Protein Kinase
    Jill M Lahti; Fiscal Year: 2010
    ..What is the function of the CK11p110 isoform in the developing embryo? Is it possible to obtain viable embryos if only CDK11p110 or CDK11 is ablated? If so, are these mice more prone to tumors or developmental defects? ..
  59. Hu proteins as novel splicing regulators in neurons
    Hua Lou; Fiscal Year: 2009
    ..The CNS neuronal differentiation system to be developed will serve as a valuable new alternative model in studies of neuron-specific splicing regulation. ..
  60. The coupling of mRNA transcription and 3' end formation
    Claire L Moore; Fiscal Year: 2010
    ..Consequently, we expect that information gained from our proposed studies will be directly applicable to human biology and medicine. ..
  61. The Role of SWI/SNF Alternative Splicing in Cancer
    ELAINE MARIE OBERLICK; Fiscal Year: 2013
    ..This proposal also will further the understanding of splicing regulation and how this intricate process is controlled. ..
  62. Functional RNA elements in the human genome
    EUGENE WEI MING YEO; Fiscal Year: 2013
    ..This research has the potential to fundamentally change our view on splicing control and its contribution to human disease. ..
  63. ALTERNATIVE MRNA PROCESSING DURING SPERMATOGENESIS
    PETER CHALLONER; Fiscal Year: 1992
    ..Ultimately, these in vitro polyadenylation and splicing reactions will provide a means of determining which trans-acting factors and cis-acting elements are necessary for alternative pre-mRNA processing in spermatids...
  64. POLYADENYLATION OF MESSENGER RNA PRECURSORS REGULATION
    PHILLIP SHARP; Fiscal Year: 1990
    Polyadenylation of messenger RNA precursors is a critical step in the synthesis of mRNAs in eucaryotic organisms and an event that is regulated for some transcription units...
  65. FUNCTIONAL SPLICEOSOME AND EXTRINSIC SPLICING FACTORS
    Ren Jang Lin; Fiscal Year: 2006
    ..We will analyze the splicing machinery when DBP2 function is impaired in vivo or in vitro. The proposed study shall reveal the dynamic features and the remodeling of the spliceosome core in yeast and human. ..
  66. EDITING OF THYMIDYLATE SYNTHASE RNA
    BRUCE DOLNICK; Fiscal Year: 2002
    ..4. Generate rTSalpha-antisense impotent cell lines and study the effect of attenuating or eliminating antisense RNA on regulation of TS gene expression and drug sensitivity. ..
  67. REGULATION OF ALTERNATIVE PROCESSING OF CALCITONIN/CGRP
    Susan Berget; Fiscal Year: 2002
    ..The overall goal of these experiments is to understand how an enhancer resembling an exon participates in both polyadenylation and splicing of neighboring exons. ..
  68. Generation of interfering RNA molecules by trans-splicing
    COLETTE COTE; Fiscal Year: 2006
    ..Thus the regulation provided by SMaRT RNAi establishes the groundwork for a new generation of conditional knockdown model systems and potential therapeutic modalities with global applications in human disease. [unreadable] [unreadable]..
  69. Mechanisms Regulating Alternative pre-mRNA Splicing
    James Patton; Fiscal Year: 2005
    ..Overall, the experiments in this proposal seek to understand the mechanistic basis underlying the repression and activation of splicing by SR proteins and hnRNP proteins. ..
  70. GENERAL PRE-MRNA SPLICING FACTORS IN DROSOPHILA
    Donald Rio; Fiscal Year: 2001
    ..Because many human diseases, such as beta-thalassemia, results from defects in pre-mRNA splicing, it is likely that alternative splicing defects may lead to oncogenic transformation of certain somatic cell types. ..
  71. Upregulation of soluble TNFR2 as treatment for Rheumatoid Arthritis
    Peter Sazani; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  72. MECHANISMS OF PREMRNA SPLICING
    THOMAS MANIATIS; Fiscal Year: 2001
    ..When completed, the proposed studies will significantly advance the understanding of the mechanisms of RNA splicing and editing. ..
  73. Structure and function of the U3 RNA-protein complex
    Carl C Correll; Fiscal Year: 2010
    ....
  74. INTERACTION OF K PROTEIN WITH PROTEIN KINASES
    Karol Bomsztyk; Fiscal Year: 2007
    ..Exploring the mechanisms and rote of K protein mitogen-induced recruitment to inducible gene loci will provide new insight into the regulation of gene expression. ..