ribonuclease iii

Summary

Summary: An endoribonuclease that is specific for double-stranded RNA. It plays a role in POST-TRANSCRIPTIONAL RNA PROCESSING of pre-RIBOSOMAL RNA and a variety of other RNA structures that contain double-stranded regions.

Top Publications

  1. 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
  2. ncbi Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes
    Christian Matranga
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cell 123:607-20. 2005
  3. pmc SMAD proteins control DROSHA-mediated microRNA maturation
    Brandi N Davis
    Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Nature 454:56-61. 2008
  4. pmc A dicer-independent miRNA biogenesis pathway that requires Ago catalysis
    Sihem Cheloufi
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA
    Nature 465:584-9. 2010
  5. 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
  6. doi A human snoRNA with microRNA-like functions
    Christine Ender
    Center for Integrated Protein Science Munich CIPSM, Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Mol Cell 32:519-28. 2008
  7. pmc MicroRNA genes are transcribed by RNA polymerase II
    Yoontae Lee
    Institute of Molecular Biology and Genetics and School of Biological Science, Seoul National University, Seoul, Korea
    EMBO J 23:4051-60. 2004
  8. pmc A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence
    Joshua J Forman
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 105:14879-84. 2008
  9. 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
  10. ncbi A microRNA in a multiple-turnover RNAi enzyme complex
    Gyorgy Hutvagner
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA
    Science 297:2056-60. 2002

Detail Information

Publications260 found, 100 shown here

  1. 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...
  2. ncbi Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes
    Christian Matranga
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cell 123:607-20. 2005
    ..For siRNAs, virtually all RISC is assembled through this cleavage-assisted mechanism. In contrast, passenger-strand cleavage is not important for the incorporation of miRNAs that derive from mismatched duplexes...
  3. pmc SMAD proteins control DROSHA-mediated microRNA maturation
    Brandi N Davis
    Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Nature 454:56-61. 2008
    ....
  4. pmc A dicer-independent miRNA biogenesis pathway that requires Ago catalysis
    Sihem Cheloufi
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA
    Nature 465:584-9. 2010
    ..Our findings link the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development...
  5. 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...
  6. doi A human snoRNA with microRNA-like functions
    Christine Ender
    Center for Integrated Protein Science Munich CIPSM, Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Mol Cell 32:519-28. 2008
    ..We further identify a number of human snoRNAs with microRNA (miRNA)-like processing signatures. We have, therefore, identified a class of small RNAs in human cells that originate from snoRNAs and can function like miRNAs...
  7. pmc MicroRNA genes are transcribed by RNA polymerase II
    Yoontae Lee
    Institute of Molecular Biology and Genetics and School of Biological Science, Seoul National University, Seoul, Korea
    EMBO J 23:4051-60. 2004
    ..These data indicate that pol II is the main, if not the only, RNA polymerase for miRNA gene transcription. Our study offers a basis for understanding the structure and regulation of miRNA genes...
  8. pmc A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence
    Joshua J Forman
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 105:14879-84. 2008
    ..As more genomes are sequenced, the methodological approach that we used for identifying motifs with high sequence conservation will be increasingly valuable for detecting functional sequence motifs within coding regions...
  9. 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...
  10. ncbi A microRNA in a multiple-turnover RNAi enzyme complex
    Gyorgy Hutvagner
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA
    Science 297:2056-60. 2002
    ..Each let-7-containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells...
  11. pmc RNAi-mediated targeting of heterochromatin by the RITS complex
    Andre Verdel
    Department of Cell Biology, Harvard Medical School, Boston, MA02115, USA
    Science 303:672-6. 2004
    ..The results suggest a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci...
  12. doi Biogenesis of small RNAs in animals
    V Narry Kim
    School of Biological Sciences and Center for National Creative Research, Seoul National University, Seoul, 151 742, Korea
    Nat Rev Mol Cell Biol 10:126-39. 2009
    ..This Review summarizes our current knowledge of how these intriguing molecules are generated in animal cells...
  13. pmc Deep-sequencing of human Argonaute-associated small RNAs provides insight into miRNA sorting and reveals Argonaute association with RNA fragments of diverse origin
    Alexander Maxwell Burroughs
    Omics Science Center, RIKEN Yokohama Institute, Yokohama shi, Kanagawa, Japan
    RNA Biol 8:158-77. 2011
    ..Finally, we observe antisense miRNA transcripts are frequently present in low copy numbers across a range of diverse miRNA loci and these transcripts appear to associate with AGO proteins...
  14. pmc The tumor suppressor microRNA let-7 represses the HMGA2 oncogene
    Yong Sun Lee
    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA
    Genes Dev 21:1025-30. 2007
    ....
  15. pmc An endogenous small interfering RNA pathway in Drosophila
    Benjamin Czech
    Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 453:798-802. 2008
    ..These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles...
  16. pmc Antagonistic role of hnRNP A1 and KSRP in the regulation of let-7a biogenesis
    Gracjan Michlewski
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK
    Nat Struct Mol Biol 17:1011-8. 2010
    ..Finally, hnRNP A1 binding to let-7a interferes with the binding of KSRP, which is known to promote let-7a biogenesis. We propose that hnRNP A1 and KSRP have antagonistic roles in the post-transcriptional regulation of let-7a expression...
  17. pmc Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs
    Christian Cole
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    RNA 15:2147-60. 2009
    ..Moreover, we showed that the processing of small RNAs derived from tRNA(Gln) is dependent on Dicer in vivo and that Dicer cleaves the tRNA in vitro...
  18. pmc DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
    Hiroki Kaneko
    Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, Kentucky 40506, USA
    Nature 471:325-30. 2011
    ..These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness...
  19. ncbi Hierarchical action and inhibition of plant Dicer-like proteins in antiviral defense
    Angelique Deleris
    Institut de Biologie Moleculaire des Plantes, CNRS Unité Propre de Recherche UPR 2357, 12, rue du Général Zimmer, 67084 Strasbourg Cedex, France
    Science 313:68-71. 2006
    ..These findings define a molecular framework for studying antiviral silencing and defense in plants...
  20. pmc Dicer, Drosha, and outcomes in patients with ovarian cancer
    William M Merritt
    University of Texas M D Anderson Cancer Center, Houston, TX 77230, USA
    N Engl J Med 359:2641-50. 2008
    ..We studied Dicer and Drosha, components of the RNA-interference machinery, in ovarian cancer...
  21. pmc DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal
    Yangming Wang
    Developmental and Stem Cell Biology Program, Department of Urology, University of California, San Francisco, California 94143, USA
    Nat Genet 39:380-5. 2007
    ..Our findings indicate that miRNAs function in the silencing of ES cell self-renewal that normally occurs with the induction of differentiation...
  22. ncbi Role for a bidentate ribonuclease in the initiation step of RNA interference
    E Bernstein
    Cold Spring Harbor Laboratory, New York 11724, USA
    Nature 409:363-6. 2001
    ..The enzyme has a distinctive structure, which includes a helicase domain and dual RNase III motifs. Dicer also contains a region of homology to the RDE1/QDE2/ARGONAUTE family that has been genetically linked to RNAi...
  23. ncbi The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis
    Markus Landthaler
    Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, NY 10021, USA
    Curr Biol 14:2162-7. 2004
    ..Our results suggest that DGCR8 and Drosha interact in human cells and reside in a functional pri-miRNA processing complex...
  24. ncbi Structural basis for double-stranded RNA processing by Dicer
    Ian J Macrae
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Science 311:195-8. 2006
    ..Dicer enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the two catalytic ribonuclease III (RNase III) domains by a flat, positively charged surface...
  25. pmc The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs
    Michele Trabucchi
    Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, California 92093 0648, USA
    Nature 459:1010-4. 2009
    ....
  26. pmc miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex
    Davide De Pietri Tonelli
    Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Development 135:3911-21. 2008
    ..5. Our results support the emerging concept that progenitors are less dependent on miRNAs than their differentiated progeny, and raise interesting perspectives as to the expansion of somatic stem cells...
  27. pmc Posttranscriptional crossregulation between Drosha and DGCR8
    Jinju Han
    School of Biological Sciences and National Creative Research Center, Seoul National University, Seoul 151 742, Korea
    Cell 136:75-84. 2009
    ..Our study reveals a previously unsuspected function of Microprocessor in mRNA stability control...
  28. pmc Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans
    R F Ketting
    The Hubrecht Laboratory and Center for Biomedical Genetics, Uppsalalaan 8, Utrecht, The Netherlands
    Genes Dev 15:2654-9. 2001
    ..dcr-1 mutants show a defect in RNAi. Furthermore, a combination of phenotypic abnormalities and RNA analysis suggests a role for dcr-1 in a regulatory pathway comprised of small temporal RNA (let-7) and its target (e.g., lin-41)...
  29. ncbi R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway
    Qinghua Liu
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Science 301:1921-5. 2003
    ..These results indicate that R2D2 bridges the initiation and effector steps of the Drosophila RNAi pathway by facilitating siRNA passage from Dicer to RISC...
  30. pmc RNAi in budding yeast
    Ines A Drinnenberg
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Science 326:544-50. 2009
    ..These results identify a previously unknown class of Dicer proteins, bring the tool of RNAi to the study of budding yeasts, and bring the tools of budding yeast to the study of RNAi...
  31. pmc Aberrant T cell differentiation in the absence of Dicer
    Stefan A Muljo
    The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    J Exp Med 202:261-9. 2005
    ..Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage...
  32. ncbi Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis
    Junjie Li
    Department of Botany and Plant Sciences, Institute of Integrative Genome Research, University of California, Riverside, Riverside, California 92508, USA
    Curr Biol 15:1501-7. 2005
    ..We conclude that 3'-end methylation is a common step in miRNA and siRNA metabolism and likely protects the 3' ends of the small RNAs from the uridylation activity...
  33. ncbi Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs
    Rui Yi
    Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10021, USA
    Nat Genet 38:356-62. 2006
    ..Here we characterize miRNAs in skin, the existence of which was hitherto unappreciated, and demonstrate their differential expression and importance in the morphogenesis of epithelial tissues within this vital organ...
  34. ncbi Reduced expression of Dicer associated with poor prognosis in lung cancer patients
    Yoko Karube
    Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan
    Cancer Sci 96:111-5. 2005
    ....
  35. pmc Genomic profiling of microRNA and messenger RNA reveals deregulated microRNA expression in prostate cancer
    Stefan Ambs
    Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4258, USA
    Cancer Res 68:6162-70. 2008
    ..In summary, microRNA expression becomes altered with the development and progression of prostate cancer. Some of these microRNAs regulate the expression of cancer-related genes in prostate cancer cells...
  36. pmc The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease
    Mark M W Chong
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
    J Exp Med 205:2005-17. 2008
    ..Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity...
  37. ncbi MicroRNAs regulate brain morphogenesis in zebrafish
    Antonio J Giraldez
    Developmental Genetics Program, Skirball Institute of Biomolecular Medicine and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA
    Science 308:833-8. 2005
    ..miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains...
  38. 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...
  39. 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...
  40. doi Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration
    Sébastien S Hébert
    Centre de Recherche du CHUQ CHUL, Axe Neurosciences, Quebec, Canada
    Hum Mol Genet 19:3959-69. 2010
    ..In summary, these results support the hypothesis that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation...
  41. pmc Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus
    Tigwa H Davis
    Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143 0730, USA
    J Neurosci 28:4322-30. 2008
    ....
  42. doi MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells
    Lasse Sinkkonen
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland
    Nat Struct Mol Biol 15:259-67. 2008
    ..The defective DNA methylation can be rescued by ectopic expression of de novo Dnmts or by transfection of the miR-290 cluster miRNAs, indicating that de novo DNA methylation in ES cells is controlled by miRNAs...
  43. pmc Diverse pathways generate microRNA-like RNAs and Dicer-independent small interfering RNAs in fungi
    Heng Chi Lee
    Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Cell 38:803-14. 2010
    ..Taken together, these results uncover several pathways for small RNA production in filamentous fungi, shedding light on the diversity and evolutionary origins of eukaryotic small RNAs...
  44. doi Posttranscriptional regulation of microRNA biogenesis in animals
    Haruhiko Siomi
    Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Mol Cell 38:323-32. 2010
    ..Here, we discuss recent studies that shed light on how multiple steps in the miRNA biogenesis pathway are regulated to modulate miRNA function in animals...
  45. ncbi RNA silencing in plants
    David Baulcombe
    The Sainsbury Laboratory, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
    Nature 431:356-63. 2004
    ..We are now in a good position to investigate the full extent of this functional diversity in genetic and epigenetic mechanisms of genome control...
  46. pmc siRNA repositioning for guide strand selection by human Dicer complexes
    Cameron L Noland
    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Mol Cell 43:110-21. 2011
    ..These results support a model in which Dicer employs two distinct RNA-binding sites-one for dsRNA processing and the other for sensing of siRNA thermodynamic asymmetry-during RISC loading in humans...
  47. doi A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function
    Sonia A Melo
    Cancer Epigenetics Laboratory, Spanish National Cancer Research Centre CNIO, 28029 Madrid, Spain
    Nat Genet 41:365-70. 2009
    ..Most important, the TRBP impairment is associated with a destabilization of the DICER1 protein. These results provide, for a subset of human tumors, an explanation for the observed defects in the expression of mature miRNAs...
  48. pmc Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells
    Megha Ghildiyal
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Science 320:1077-81. 2008
    ..We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line...
  49. ncbi Dicer is essential for mouse development
    Emily Bernstein
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Genet 35:215-7. 2003
    ..Coupled with our inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggests a role for Dicer, and, by implication, the RNAi machinery, in maintaining the stem cell population during early mouse development...
  50. pmc RNA sequence analysis defines Dicer's role in mouse embryonic stem cells
    J Mauro Calabrese
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 104:18097-102. 2007
    ..The results presented suggest a model in which repeat-associated miRNAs serve as host defenses against repetitive elements, a function canonically ascribed to other classes of short RNA...
  51. 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...
  52. pmc In vitro reconstitution of the human RISC-loading complex
    Ian J Macrae
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 105:512-7. 2008
    ..Furthermore, once Ago2 is loaded with an miRNA, it tends to dissociate from the rest of the complex. These results lay the groundwork for future structural and functional dissection of RISC loading in humans...
  53. ncbi Processing of primary microRNAs by the Microprocessor complex
    Ahmet M Denli
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 432:231-5. 2004
    ..Considered together, these results indicate a role for Pasha in miRNA maturation and miRNA-mediated gene regulation...
  54. pmc Small RNAs derived from snoRNAs
    Ryan J Taft
    Australian Research Council Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia
    RNA 15:1233-40. 2009
    ..These findings indicate that there is interplay between the RNA silencing and snoRNA-mediated RNA processing systems, and that sdRNAs comprise a novel and ancient class of small RNAs in eukaryotes...
  55. pmc Conserved vertebrate mir-451 provides a platform for Dicer-independent, Ago2-mediated microRNA biogenesis
    Jr Shiuan Yang
    Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:15163-8. 2010
    ..Beyond the demonstration of an alternative strategy to direct gene silencing, these observations open the way for transgenic rescue of Dicer conditional knockouts...
  56. pmc A role for noncanonical microRNAs in the mammalian brain revealed by phenotypic differences in Dgcr8 versus Dicer1 knockouts and small RNA sequencing
    Joshua E Babiarz
    The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143, USA
    RNA 17:1489-501. 2011
    ..Taken together, our findings provide evidence for a diverse population of highly expressed noncanonical miRNAs that together are likely to play important functional roles in post-mitotic neurons...
  57. doi Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage
    Sergei B Koralov
    Immune Disease Institute and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Cell 132:860-74. 2008
    ....
  58. pmc TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing
    Astrid D Haase
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4508 Basel, Switzerland
    EMBO Rep 6:961-7. 2005
    ..The TRBP-Dicer interaction shown raises interesting questions about the potential interplay between RNAi and interferon-PKR pathways...
  59. ncbi The Microprocessor complex mediates the genesis of microRNAs
    Richard I Gregory
    The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    Nature 432:235-40. 2004
    ..In vivo knock-down and in vitro reconstitution studies revealed that both components of this smaller complex, termed Microprocessor, are necessary and sufficient in mediating the genesis of miRNAs from the primary miRNA transcript...
  60. 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
    ..in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases...
  61. pmc Structural insights into RNA processing by the human RISC-loading complex
    Hong Wei Wang
    Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA
    Nat Struct Mol Biol 16:1148-53. 2009
    ..A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2...
  62. doi A three-dimensional view of the molecular machinery of RNA interference
    Martin Jinek
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Nature 457:405-12. 2009
    ..The molecular structures of Dicer and the Argonaute proteins, free and bound to small RNAs, have offered exciting insights into the molecular mechanisms that are central to RNA silencing pathways...
  63. pmc The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster
    Ronald P Van Rij
    Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA
    Genes Dev 20:2985-95. 2006
    ..Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila...
  64. ncbi Single processing center models for human Dicer and bacterial RNase III
    Haidi Zhang
    Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
    Cell 118:57-68. 2004
    ..Based on these and other data, we propose that Dicer functions through intramolecular dimerization of its two RNase III domains, assisted by the flanking RNA binding domains, PAZ and dsRBD...
  65. 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...
  66. pmc Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants
    Jr Shiuan Yang
    Department of Developmental Biology, Sloan Kettering Institute, 1275 York Avenue, Box 252, New York, NY 10065, USA
    Mol Cell 43:892-903. 2011
    ..Nevertheless, ongoing studies reveal a growing number of settings in which alternative microRNA pathways contribute to distinct phenotypes among core microRNA biogenesis mutants...
  67. 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...
  68. pmc Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing
    Chryssa Kanellopoulou
    The Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 19:489-501. 2005
    ..Our data suggest that Dicer participates in multiple, fundamental biological processes in a mammalian organism, ranging from stem cell differentiation to the maintenance of centromeric heterochromatin structure and centromeric silencing...
  69. pmc Differential regulation of microRNA stability
    Sophie Bail
    Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854 8082, USA
    RNA 16:1032-9. 2010
    ..The development of a biochemically amendable system to analyze the mechanism of differential miRNA stability provides an important step in efforts to regulate gene expression by modulating miRNA stability...
  70. ncbi Negative feedback regulation of Dicer-Like1 in Arabidopsis by microRNA-guided mRNA degradation
    Zhixin Xie
    Center for Gene Research and Biotechnology, Oregon State University, Corvallis, OR 97331, USA
    Curr Biol 13:784-9. 2003
    ..These results indicate that DCL1 mRNA is subject to negative feedback regulation through the activity of a miRNA...
  71. pmc TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs
    Xiaohua Su
    Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
    Nature 467:986-90. 2010
    ....
  72. pmc CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III
    Elitza Deltcheva
    The Laboratory for Molecular Infection Medicine Sweden, Umea, Sweden
    Nature 471:602-7. 2011
    ..pyogenes against prophage-derived DNA. Our study reveals a novel pathway of small guide RNA maturation and the first example of a host factor (RNase III) required for bacterial RNA-mediated immunity against invaders...
  73. pmc The loop position of shRNAs and pre-miRNAs is critical for the accuracy of dicer processing in vivo
    Shuo Gu
    Departments of Pediatrics and Genetics, Stanford University, Stanford, CA 94305, USA
    Cell 151:900-11. 2012
    ..This has important implications for both miRNA processing and future design of shRNAs for RNAi-based genetic screens and therapies...
  74. doi Dicer recognizes the 5' end of RNA for efficient and accurate processing
    Jong Eun Park
    School of Biological Sciences, Seoul National University, Seoul 151 742, Korea
    Nature 475:201-5. 2011
    ..Thus, 5'-end recognition by Dicer is important for precise and effective biogenesis of miRNAs. Insights from this study should also afford practical benefits to the design of small hairpin RNAs...
  75. pmc Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans
    R Lu
    Institute for Integrative Genome Biology and Department of Plant Pathology, University of California, Riverside, California 92521, USA
    Nature 436:1040-3. 2005
    ..This work establishes a C. elegans model for genetic studies of animal virus-host interactions and indicates that mammals might use a siRNA pathway as an antiviral response...
  76. pmc Site-specific DICER and DROSHA RNA products control the DNA-damage response
    Sofia Francia
    IFOM Foundation FIRC Institute of Molecular Oncology Foundation, Via Adamello 16, 20139 Milan, Italy
    Nature 488:231-5. 2012
    ..Our results describe an unanticipated direct role of a novel class of ncRNAs in the control of DDR activation at sites of DNA damage...
  77. pmc Genome-wide antisense transcription drives mRNA processing in bacteria
    Iñigo Lasa
    Laboratory of Microbial Biofilms, Instituto de Agrobiotecnologia, Consejo Superior de Investigaciones Científicas Universidad Pública de Navarra Gobierno de Navarra, 31006 Pamplona, Spain
    Proc Natl Acad Sci U S A 108:20172-7. 2011
    ....
  78. 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...
  79. pmc Critical roles for Dicer in the female germline
    Elizabeth P Murchison
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA
    Genes Dev 21:682-93. 2007
    ..Our studies identify Dicer as central to a regulatory network that controls oocyte gene expression programs and that promotes genomic integrity in a cell type notoriously susceptible to aneuploidy...
  80. doi Modulation of microRNA processing by p53
    Hiroshi I Suzuki
    Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 460:529-33. 2009
    ..Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology...
  81. pmc DGCR8 HITS-CLIP reveals novel functions for the Microprocessor
    Sara Macias
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
    Nat Struct Mol Biol 19:760-6. 2012
    ..These data provide insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs...
  82. pmc The RNA-binding proteins HYL1 and SE promote accurate in vitro processing of pri-miRNA by DCL1
    Zhicheng Dong
    Biology Department and Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 105:9970-5. 2008
    ..We show that recombinant HYL1 and SE proteins accelerate the rate of DCL1-mediated cleavage of pre- and pri-miR167b substrates and promote accurate processing...
  83. pmc Beyond secondary structure: primary-sequence determinants license pri-miRNA hairpins for processing
    Vincent C Auyeung
    Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
    Cell 152:844-58. 2013
    ..elegans pri-miRNAs imparted efficient processing in human cells, thereby confirming the importance of primary-sequence determinants for distinguishing pri-miRNAs from other hairpin-containing transcripts...
  84. ncbi A hexanucleotide element directs microRNA nuclear import
    Hun Way Hwang
    Program in Human Genetics and Molecular Biology, McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Science 315:97-100. 2007
    ..Our results indicate that miRNAs sharing common 5' sequences, considered to be largely redundant, might have distinct functions because of the influence of cis-acting regulatory motifs...
  85. pmc MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis
    Katsuhiko Hayashi
    Wellcome Trust Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    PLoS ONE 3:e1738. 2008
    ..Although it has been clear that piRNAs play a role in repression of retrotransposons during spermatogenesis, the function of miRNA in mouse germ cells has been unclear...
  86. pmc MicroRNA-373 induces expression of genes with complementary promoter sequences
    Robert F Place
    Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA
    Proc Natl Acad Sci U S A 105:1608-13. 2008
    ..In conclusion, we have identified a miRNA that targets promoter sequences and induces gene expression. These findings reveal a new mode by which miRNAs may regulate gene expression...
  87. pmc Dicer1 functions as a haploinsufficient tumor suppressor
    Madhu S Kumar
    Massachusetts Institute of Technology Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts 02139, USA
    Genes Dev 23:2700-4. 2009
    ..These findings suggest Dicer1 may be an important haploinsufficient tumor suppressor gene and, furthermore, that other factors controlling miRNA biogenesis may also function in this manner...
  88. pmc The interaction between DCL1 and HYL1 is important for efficient and precise processing of pri-miRNA in plant microRNA biogenesis
    Yukio Kurihara
    Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba 3 8 1, Meguro ku, Tokyo 153 8902, Japan
    RNA 12:206-12. 2006
    ..These results indicate that HYL1 has a function in assisting efficient and precise cleavage of pri-miRNA through interaction with DCL1...
  89. doi Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage
    M S Anglesio
    Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
    J Pathol 229:400-9. 2013
    ..We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations...
  90. ncbi Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs
    Antonio J Giraldez
    Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA
    Science 312:75-9. 2006
    ..We also show that miR-430 accelerates the deadenylation of target mRNAs. These results suggest that miR-430 facilitates the deadenylation and clearance of maternal mRNAs during early embryogenesis...
  91. pmc The colorectal microRNAome
    Jordan M Cummins
    The Sidney Kimmel Comprehensive Cancer Center and Howard Hughes Medical Institute, Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 103:3687-92. 2006
    ..These studies suggest that the human genome contains many more miRNAs than currently identified and provide an approach for the large-scale experimental cloning of novel human miRNAs in human tissues...
  92. 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...
  93. pmc Mammalian microRNAs: experimental evaluation of novel and previously annotated genes
    H Rosaria Chiang
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
    Genes Dev 24:992-1009. 2010
    ....
  94. pmc Identification of nuclear dicing bodies containing proteins for microRNA biogenesis in living Arabidopsis plants
    Yuda Fang
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Curr Biol 17:818-23. 2007
    ..On the basis of these data, we propose that D-bodies are crucial for orchestrating pri-miRNA processing and/or storage/assembly of miRNA-processing complexes in the nuclei of plant cells...
  95. pmc Dicer is associated with ribosomal DNA chromatin in mammalian cells
    Lasse Sinkkonen
    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    PLoS ONE 5:e12175. 2010
    ..Components of the RNA silencing machinery are involved in different aspects of chromatin function in numerous organisms. However, association of RNA silencing with chromatin in mammalian cells remains unclear...
  96. 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...
  97. pmc Arabidopsis primary microRNA processing proteins HYL1 and DCL1 define a nuclear body distinct from the Cajal body
    Liang Song
    Biology Department and Huck Institute of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 104:5437-42. 2007
    ..Thus, the distinct HYL1- and DCL1-containing nuclear bodies may be miRNA precursor processing sites. Alternatively, they may be assembly and storage sites for the miRNA precursor processing machinery...
  98. ncbi Impaired microRNA processing enhances cellular transformation and tumorigenesis
    Madhu S Kumar
    MIT Center for Cancer Research, Cambridge, Massachusetts 02139, USA
    Nat Genet 39:673-7. 2007
    ..Furthermore, conditional deletion of Dicer1 enhanced tumor development in a K-Ras-induced mouse model of lung cancer. Overall, these studies indicate that abrogation of global miRNA processing promotes tumorigenesis...
  99. pmc Dicer partner proteins tune the length of mature miRNAs in flies and mammals
    Ryuya Fukunaga
    Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA
    Cell 151:533-46. 2012
    ..Thus, Dicer-binding partner proteins change the choice of cleavage site by Dicer, producing miRNAs with target specificities different from those made by Dicer alone or Dicer bound to alternative protein partners...
  100. pmc RNase G (CafA protein) and RNase E are both required for the 5' maturation of 16S ribosomal RNA
    Z Li
    Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, FL 33101, USA
    EMBO J 18:2878-85. 1999
    ..These data indicate that both RNase E and CafA protein are required for a two step, sequential maturation of the 5' end of 16S rRNA, and that CafA protein is a new ribonuclease. We propose that it be renamed RNase G...
  101. pmc Selective blockade of microRNA processing by Lin28
    Srinivas R Viswanathan
    Stem Cell Program, Children s Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA
    Science 320:97-100. 2008
    ..Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers...

Research Grants72

  1. Regulation of an Iron Import Facilitator by Transcriptional Interference
    CAMILLE REYES NERY; Fiscal Year: 2010
    ....
  2. miRNAs and epidermal langerhans cell development and function
    Qing Sheng Mi; Fiscal Year: 2011
    ..The ribonuclease III enzyme Dicer is required for the processing of mature and functional miRNAs...
  3. Reactivity epitopes of ribonuclease III substrates
    ALLEN WHITALL NICHOLSON; Fiscal Year: 2010
    ..dsRNA cleavage is catalyzed by members of the ribonuclease III (RNase III) family of endoribonucleases, which are highly conserved in bacterial and eukaryotic cells...
  4. Regulation of Leydig cell function by small noncoding RNAs
    Wei Yan; Fiscal Year: 2013
    ..Future investigation based upon this pilot study may lead to novel diagnostics and treatments for male infertility due to endocrine disorders, and miRNAs may represent a novel class of male contraceptive agents. ..
  5. The functional role of DRH-1 in RNAi directed viral immunity
    Rui Lu; Fiscal Year: 2013
    ..Novel findings from the proposed studies may also shed light on some nematode-specific features of RDVI since DRH-1 is not conserved in fungi, plants or insects. ..
  6. Global analysis of mRNA decay in Bacillus subtilis
    David H Bechhofer; Fiscal Year: 2013
    ..Elucidating the mechanism of mRNA decay could lead to the design of antibiotics that inhibit this essential process and thereby prevent bacterial colonization of human tissues. ..
  7. Understanding microRNA Biogenesis and Function
    Phillip D Zamore; Fiscal Year: 2013
    ..discovered in 1993 and the study of their biogenesis began in 2001 with the discovery that the multi-domain ribonuclease III (RNase III) enzyme Dicer converts miRNA precursors (pre-miRNAs) into mature miRNAs...
  8. Analysis of the Molecular Machinery of microRNA-processing pathways
    Daniel Cifuentes; Fiscal Year: 2013
    ..It is fully expected that Dr. Cifuentes will be competitive for such group leader appointments at the completion of his Career Development Award, tailored to enhance his scientific and mentoring skills. ..
  9. Stress and proliferation states impact microRNA-mediated regulation in cancer
    Phillip A Sharp; Fiscal Year: 2013
    ..And fourth, we will investigate the function of Argonaute that is essential for viability in embryonic stem cells defective for synthesis of miRNAs, i.e. null for Dicer!" " ..
  10. RNases and RNA Metabolism in Bacteria
    Murray P Deutscher; Fiscal Year: 2013
    ..We anticipate that the studies detailed in this proposal will provide important, new information on the enzymes, factors and processes that encompass RNA metabolism. ..
  11. Specificity of miRNA Processing Provided by Double-Stranded RNA Binding Domains
    Scott A Showalter; Fiscal Year: 2013
    ..The full molecular understanding of miRNA processing proposed herein will allow novel entry points for targeted manipulation of miRNA expression, which may have broad impacts on both basic and clinical science. ..
  12. Molecular Characterization of the microRNA Processing Pathways
    ANTONIO GIRALDEZ; Fiscal Year: 2013
    ....
  13. Analysis of E. coli ribonucleases and RNA metabolism
    Sidney R Kushner; Fiscal Year: 2013
    ..Information gained from this work could be instrumental in the identification of potential new drug targets. ..
  14. MITOCHONDRIAL DNA OF NORMAL AND MUTANT TRYPANOSOMES
    Kenneth D Stuart; Fiscal Year: 2013
    ..These studies will determine whether PTMs regulates steps in editing and editing between life cycle stages. Overall, the project will expand the understanding of a process that is essential for the parasite and may provide drug targets. ..
  15. Non-canonical miRNA biogenesis mechanisms in Drosophila and mammals
    Eric C Lai; Fiscal Year: 2013
    ..abstract_text> ..
  16. Ribonuclease III mechanism of double-strand RNA cleavage
    ALLEN NICHOLSON; Fiscal Year: 2003
    ..The most studied member of the RNase III superfamily is Escherichia coli ribonuclease III and there has been recent significant progress in determining the E. coil RNase Ill mechanism of action...
  17. Structural studies of exoribonucleases
    Arun Malhotra; Fiscal Year: 2007
    ..coli); these studies will complement a parallel study to completely determine and characterize the physiological role of all the exoribonucleases in E. coli, now underway in the Deutscher laboratory. ..
  18. FACTORS IN MATURATION OF SMALL RNAS IN THE YEAST NUCLEUS
    MICHAEL CULBERTSON; Fiscal Year: 2003
    ..abstract_text> ..
  19. ANALYSIS OF E COLI GTP-BINDING PROTEINS AND THEIR GENES
    PAUL MARCH; Fiscal Year: 1993
    ..the lep and rnc operons of Escherichia coli have shown that, in addition to encoding signal peptidase I and ribonuclease III respectively, they also both encode novel GTP-binding proteins...
  20. STRUCTURE/FUNCTION OF EUKARYOTIC RNASE III
    Manuel Ares; Fiscal Year: 1999
    ..Together, the proposed experiments should provide an initial characterization of a conserved and fundamental eukaryotic gene product about which little is known. ..
  21. PROCESSING OF RNA IN E. COLI AND PHAGE T4
    DAVID APIRION; Fiscal Year: 1990
    ..The experiments will be carried out by using columns, gel electrophoresis, chromatography and various other techniques...
  22. Mda-5: Novel Apoptosis Inducing Gene
    Paul Fisher; Fiscal Year: 2007
    ..Additionally, based on its chromosomal location, 2q24, the present studies could also shed light on a potential role of mda-5 in specific cancer etiologies as well as enhance our appreciation of the carcinogenic process. ..
  23. PURCHASE OF A 600 MHZ NMR SPECTROMETER
    John SantaLucia; Fiscal Year: 2001
    ..Students are trained from elementary NMR through advanced theory, including density matrix and product operator descriptions of NMR and pulse sequence programming...
  24. Characterization of TRBP-containing complexes
    Ramin Shiekhattar; Fiscal Year: 2009
    ..Aim 3 extends the work to the analysis of the large TRBP- containing complex, which is associated with the 60S ribosome subunit and the human Armitage protein involved in translational repression. ..
  25. HCV INTERNAL RIBOSOME ENTRY SITE AS TARGET FOR THERAPY
    Hugh Robertson; Fiscal Year: 2003
    ..Included will be design and testing of External Guide Sequences (EGSs) for human RNase P in liver cells. ..
  26. Generation of a potent kinase siRNA library using Dicer
    Zairen Sun; Fiscal Year: 2005
    ..We believe that our technology platform is reliable and innovative, and the outcome of this project will be assuredly a commercial success. ..
  27. HIV-1 TROPISM AND CHEMOKINE RECEPTORS
    BRYAN CULLEN; Fiscal Year: 2002
    ..The final specific aim focusses on the promoter regions of CCR5, the identification of transcription factors that may interact with the promoter, and the use of antisense strategies to block CCR5 expression. ..
  28. Role of BMPRII Mutants in the Pathogenesis of Pulmonary Hypertension
    Akiko Hata; Fiscal Year: 2009
    ....
  29. The Role of TIMP-1 in Uterine Physiology
    Warren Nothnick; Fiscal Year: 2005
    ..These studies will broaden our understanding on the role of TIMP-1 in uterine physiology and may help to develop new strategies to treat uterine disorders such as infertility, endometriosis and uterine cancer. ..
  30. Regulation of human microRNA biosynthesis and activity
    BRYAN CULLEN; Fiscal Year: 2007
    ..Finally, in specific aim 5, we seek to extend our exciting initial data demonstrating inhibition of miRNA function by the adenovirus VA1 non-coding RNA by trying to define the underlying mechanism. ..
  31. Estrogen regulation of uterine microRNAs: Novel factors in MMP-9 regulation
    Warren Nothnick; Fiscal Year: 2008
    ..Enhancing our understanding on the regulation of MMP-9 expression may lead to the establishment of novel approaches to counteract mis-expression of this protease and the diseases associated with it. [unreadable] [unreadable] [unreadable]..
  32. Effect of APOBEC3G on retroviruses and retrotransposons
    BRYAN CULLEN; Fiscal Year: 2009
    ..abstract_text> ..
  33. Molecular Mechanism of HIV-1 Vif Function
    BRYAN CULLEN; Fiscal Year: 2007
    ..Together, this wide-ranging series of experiments should lead to considerable insight into how HIV-1 Vif functions and potentially suggest approaches to inhibit Vif function. ..
  34. Mechanisms of TGFB Signal Transduction
    Akiko Hata; Fiscal Year: 2007
    ..These studies should provide important insights into TGFbeta-mediated regulation of gene expression, which is of direct relevance to both normal physiology and a variety of disease states. ..
  35. Hemodynamic forces regulate BMPs in coronary arteries
    Zoltan Ungvari; Fiscal Year: 2009
    ..abstract_text> ..
  36. Role of PKR in Growth Regulation
    Glen Barber; Fiscal Year: 2008
    ..We propose that these aims will lend insight into mechanisms of cell signaling, tumorigenesis and interferon-mediated actions in the cell. ..
  37. Alzheimer disease biomarkers in lens
    Peter H Frederikse; Fiscal Year: 2010
    ..These studies build on our earlier studies to understand the role of AbetaPP and Abeta in the lens which are already providing a new and specific conceptual basis for understanding cataract and its links with the brain. ..
  38. Vaccination With Peptide-loaded alphaDC1s For Malignant Gliomas
    Hideho Okada; Fiscal Year: 2008
    ..Information from this pilot study will establish a basis to design subsequent trials with patient populations in which more significant clinical benefit might be realized. ..
  39. PHOTORECEPTOR CELL DEVELOPMENT AND SIGNAL TRANSDUCTION
    Richard Carthew; Fiscal Year: 2005
    ..abstract_text> ..
  40. Left/right asymmetric neuronal cell fate specification
    Oliver Hobert; Fiscal Year: 2006
    ..These studies may reveal fundamental principles of neuronal development and may shed light onto the elusive mechanisms of generating L/R asymmetry in the nervous system...
  41. CD44/VARIANT CYTOSKELETON IN BREAST CANCER PROGRESSION
    LILLY YW BOURGUIGNON; Fiscal Year: 2010
    ....
  42. Real-time PCR expression profiling of microRNA
    Thomas Schmittgen; Fiscal Year: 2006
    ..The unparallel sensitivity and specificity of real-time PCR as applied to this new and exciting class of regulatory RNAs should propel the field into new directions not only in cancer but in other areas of human health. ..
  43. RNA-Mediated Silencing: Mechanisms and Biological Roles in Chlamydomonas
    Heriberto Cerutti; Fiscal Year: 2009
    ..The overall findings are expected to improve our ability to exploit RNAi as an experimental and/or therapeutic tool, with likely impacts in both medicine and agriculture. ..
  44. Trichomonas Lipophosphoglycan in Regulation Immune Responses
    Raina Fichorova; Fiscal Year: 2008
    ..vaginalis infections and complications. [unreadable] [unreadable] [unreadable]..
  45. Myosin-mediated organelle trafficking in plants
    Valerian V Dolja; Fiscal Year: 2010
    ..abstract_text> ..
  46. Micro RNA Expression and Cancer
    Thomas Schmittgen; Fiscal Year: 2005
    ..is approximately 22 nt in length and is cleaved from partially duplexed precursors (termed pre-miRNA) by the ribonuclease III Dicer...
  47. 2007 Epigenetics Gordon Research Conference
    Steven Jacobsen; Fiscal Year: 2007
    ..Perhaps equally importantly, it will launch the careers of new scientists in this frontier area. [unreadable] [unreadable] [unreadable]..
  48. Mechanisms of VSV-mediated Oncolysis
    Glen N Barber; Fiscal Year: 2010
    ..Understanding how these pathways function has significant impact on understanding pathogenesis and for developing novel therapeutics and vaccines to combat disease. ..
  49. ALZHEIMER PATHOPHYSIOLOGY IN HUMAN CATARACT FORMATION
    PETER FREDERIKSE; Fiscal Year: 2002
    ..abstract_text> ..
  50. INITIATION OF MRNA DECAY IN BACILLUS SUBTILIS
    David H Bechhofer; Fiscal Year: 2010
    ..Elucidating the mechanism of mRNA in this bacterium could lead to the design of new antibiotics that inhibit the mRNA decay process and thereby prevent successful bacterial colonization of human tissues. ..
  51. A Link between RNAi and Fragile X Mental Retardation
    Scott Hammond; Fiscal Year: 2009
    ..While this project focuses on FMRP regulation of neuronal genes, it will provide a general framework for studies on all aspects of RNAi regulation of mammalian cellular pathways. ..
  52. Immunogenicity of Hepatitis C Virus (HCV) like particles
    Glen Barber; Fiscal Year: 2007
    ..abstract_text> ..
  53. CD44-P185HER2 INTERACTION IN OVARIAN CANCER PROGRESSION
    LILLY BOURGUIGNON; Fiscal Year: 2007
    ..abstract_text> ..
  54. Prenatal Hypoxia and Development of Insulin Resistance
    RUSSELL ANTHONY; Fiscal Year: 2006
    ..These studies will provide insight in to the role fetal hypoxia alone may play in the development of Syndrome X. [unreadable] [unreadable]..
  55. Identify and characterize novel Wnt pathway genes
    Brian Harfe; Fiscal Year: 2006
    ..The PIs have experience working with C. elegans, mice and chick model systems and are positioned to take full advantage of each system. ..
  56. Genetic Analysis of Heavy Metals Neurotoxicity
    Fen Biao Gao; Fiscal Year: 2005
    ....
  57. Variation and Quantitative Genetics in Model Organisms
    Detlef Weigel; Fiscal Year: 2004
    ..A second focus will be recent discoveries of how changes in key regulatory factors cause major phenotypic differences in more distantly related taxa. ..
  58. Stable suppression of gene function in mammals by RNAi
    Scott Hammond; Fiscal Year: 2002
    ..proposed commercial application: not available ..
  59. Centriole Orientation During Left/Right Symmetry Breaking in the Mouse
    Wallace Marshall; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  60. Hsp70 as Dispatcher of Virus Assembly and Trafficking
    VALERIAN DOLJA; Fiscal Year: 2007
    ..Functional significance of the observed interactions will be assessed using genetic strategies targeting both Hsp70h and host proteins. ..
  61. Understanding the Mechanism of RNA Interference (RNAi)
    Phillip Zamore; Fiscal Year: 2009
    ....
  62. Visualizing protein interaction networks by fluorescence complementation
    Mensur Dlakic; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  63. Animal Models For Studying Angelman Syndrome, A Developmental Brain Disorder
    Fen Biao Gao; Fiscal Year: 2008
    ..RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page J Description, [unreadable] [unreadable]..
  64. A FADD-Associated Helicase Essential for Host Defense
    Glen Barber; Fiscal Year: 2008
    ..We anticipate that these studies will improve our knowledge of pathogenesis and provide new concepts for the rational design of novel therapeutic and vaccine strategies. [unreadable] [unreadable] [unreadable]..
  65. Arboviral suppressors of RNA interference
    KEVIN MYLES; Fiscal Year: 2008
    ..The identification of suppressors of RNA silencing encoded in mosquito-borne virus genomes would have enormous implications for understanding the transmission of arthropod-borne viral diseases. [unreadable] [unreadable] [unreadable]..
  66. Small RNAs in skeletogenesis
    Tatsuya Kobayashi; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  67. Genetics of DNA Methylation Patterning of Arabidopsis
    Steven Jacobsen; Fiscal Year: 2008
    ....
  68. Small Molecule Inhibitors of Cilia
    Wallace Marshall; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  69. ENHANCING THE INTRACELLULAR FUNCTIONING OF HIV RIBOZYMES
    John Rossi; Fiscal Year: 2001
    ..The results from this program will greatly facilitate the effective use of ribozyme treatment for HIV-1 infection in a gene therapy setting. ..