Transcription of protein-coding genes in Leishmania

Summary

Principal Investigator: PETER JOHN MYLER
Abstract: Despite more than 20 years of molecular investigation. little is currently known about the essential process of the transcriptioo of protein-coding genes in Leishmania and other trypanosomatids, other than that it differs from that in other eukaryotes because mature mRNAs are generated by transspncing of large polycistronic primary transcripts. Moreover, there is no evidence fO( the transcriptional regulation of gene expression typically seen in other organisms. Previous worK from our laboratory has shown that transcription initiates at ooly a small number of sites between large (50-500 kb) divergent clusters of adjacent protein-coding genes on the same DNA strand and proceeds bi-directionally before temlination at the junction between convergent gene clusters. However, the 'promoter" elements involved in transcription inillation remain a mystery. In other eukaryotes, histone modification and chromatin re-modeling are important for activation of transcription, and recent experiments suggest that this may also be the case in trypanosomatids. This has ted us to hypothesize that the strand-switch regions between divergent PGCs recruit chromatin-remodenng complexes which modify histones and alter the local chromatin structure in these regions to allow access by the RNA polymerase II preinitiation complex, which then initiates transcription in both directions. In this proposal, we will test this hypothesis and build on our current work to further characterize the chromatin-modifying enzymes that are involved in transcription initiation.
Funding Period: ----------------2003 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Characterization of the RNA polymerase II and III complexes in Leishmania major
    Santiago Martinez-Calvillo
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109 5219, USA
    Int J Parasitol 37:491-502. 2007
  2. pmc Gene organization and sequence analyses of transfer RNA genes in Trypanosomatid parasites
    Norma E Padilla-Mejía
    Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Av de los Barrios 1, Col Los Reyes Iztacala, Tlalnepantla, Edo de Mexico, Mexico
    BMC Genomics 10:232. 2009
  3. pmc Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania
    Henri G A M van Luenen
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 150:909-21. 2012
  4. pmc Paromomycin: uptake and resistance in Leishmania donovani
    Anupam Jhingran
    School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
    Mol Biochem Parasitol 164:111-7. 2009
  5. pmc Histone acetylations mark origins of polycistronic transcription in Leishmania major
    Sean Thomas
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    BMC Genomics 10:152. 2009
  6. pmc Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei
    Bryan C Jensen
    Seattle Biomedical Research Institute, 307 Westlake Ave North, Seattle, WA 98109, USA
    BMC Genomics 10:482. 2009

Scientific Experts

  • Sean Thomas
  • Bryan C Jensen
  • Peter J Myler
  • Santiago Martinez-Calvillo
  • Henri G A M van Luenen
  • Norma E Padilla-Mejía
  • Anupam Jhingran
  • Saara Vainio
  • Anastassis Perrakis
  • Arno Velds
  • Ludo Pagie
  • Paul André Genest
  • Sabrina Jan
  • Tatjana Heidebrecht
  • Marja Nieuwland
  • Gowthaman Ramasamy
  • Carol Farris
  • Pankaj Tripathi
  • Piet Borst
  • Andrew Haydock
  • Bas van Steensel
  • Ron M Kerkhoven
  • Rosaura Hernandez-Rivas
  • Shailendra Saxena
  • Bhavna Chawla
  • Rebeca G Manning-Cela
  • Michael Peter Barrett
  • Luis E Florencio-Martínez
  • Elisa E Figueroa-Angulo
  • Rentala Madhubala
  • Aaron Leland
  • Alka Saxena
  • Amanda Green

Detail Information

Publications6

  1. pmc Characterization of the RNA polymerase II and III complexes in Leishmania major
    Santiago Martinez-Calvillo
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109 5219, USA
    Int J Parasitol 37:491-502. 2007
    ....
  2. pmc Gene organization and sequence analyses of transfer RNA genes in Trypanosomatid parasites
    Norma E Padilla-Mejía
    Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Av de los Barrios 1, Col Los Reyes Iztacala, Tlalnepantla, Edo de Mexico, Mexico
    BMC Genomics 10:232. 2009
    ..To analyze the sequences and genomic organization of tRNA genes and other Pol III-transcribed genes, we have performed an in silico analysis of the Tritryps genome sequences...
  3. pmc Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania
    Henri G A M van Luenen
    Division of Molecular Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 150:909-21. 2012
    ..We conclude that J is required for proper transcription termination and infer that the absence of internal J kills Leishmania by massive readthrough of transcriptional stops...
  4. pmc Paromomycin: uptake and resistance in Leishmania donovani
    Anupam Jhingran
    School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
    Mol Biochem Parasitol 164:111-7. 2009
    ..The drug induced reduction in membrane potential and inhibition of protein synthesis were less pronounced in the resistant strain in comparison to the wild-type...
  5. pmc Histone acetylations mark origins of polycistronic transcription in Leishmania major
    Sean Thomas
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    BMC Genomics 10:152. 2009
    ..However, the mechanism by which Kinetoplastidae initiate transcription is unclear, and promoter sequences are undefined...
  6. pmc Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei
    Bryan C Jensen
    Seattle Biomedical Research Institute, 307 Westlake Ave North, Seattle, WA 98109, USA
    BMC Genomics 10:482. 2009
    ..Trypanosomatids represent a unique case in eukaryotes in that they transcribe protein-coding genes as large polycistronic units, and rarely regulate gene expression at the level of transcription initiation...