: The overall goal is to understand in molecular detail the novel RNA modification phenomenon known as uridine insertion/deletion RNA editing that occurs in the mitochondria of kinetoplastid protists. Messenger RNA transcripts of the maxicircle mitochondrial genome must be edited after transcription by insertion and deletion of U's at multiple sites to produce translatable mRNAs. This editing involves the participation of trans- acting guide RNAs which determine the precise editing sites and mediate the precise number of U's to be added or deleted. The proposal is to identify all of the proteins and RNAs involved in this process, to determine if these proteins are required for viability by RNA interference down regulation of expression, and to express the proteins in several cell systems and analyze their enzymatic or structural properties. Reconstitution of editing activities in vitro and in vivo will be performed using recombinant proteins. Structural analysis of the major core L-complex will also be performed. A functional complementation analysis of mutated L-complex proteins will also be performed in vitro and in vivo to determine the function of specific conserved motifs. The nature of the RNA mediated interactions between the L-complex and other editing complexes will be investigated. This research should yield valuable information on a novel gene regulation mechanism that is required for viability of these important human and animal parasites.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Pathogenic Eukaryotes Study Section (PTHE)
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Rogers, Martin J
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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Simpson, Larry; Douglass, Stephen M; Lake, James A et al. (2015) Comparison of the Mitochondrial Genomes and Steady State Transcriptomes of Two Strains of the Trypanosomatid Parasite, Leishmania tarentolae. PLoS Negl Trop Dis 9:e0003841
Wong, Richard G; Kazane, Katelynn; Maslov, Dmitri A et al. (2015) U-insertion/deletion RNA editing multiprotein complexes and mitochondrial ribosomes in Leishmania tarentolae are located in antipodal nodes adjacent to the kinetoplast DNA. Mitochondrion 25:76-86
Li, Feng; Herrera, Jeremy; Zhou, Sharleen et al. (2011) Trypanosome REH1 is an RNA helicase involved with the 3'-5' polarity of multiple gRNA-guided uridine insertion/deletion RNA editing. Proc Natl Acad Sci U S A 108:3542-7
Simpson, Larry; Aphasizhev, Ruslan; Lukes, Julius et al. (2010) Guide to the nomenclature of kinetoplastid RNA editing: a proposal. Protist 161:2-6
Gao, Guanghan; Rogers, Kestrel; Li, Feng et al. (2010) Uridine insertion/deletion RNA editing in Trypanosomatids: specific stimulation in vitro of Leishmania tarentolae REL1 RNA ligase activity by the MP63 zinc finger protein. Protist 161:489-96
Osato, Daren; Rogers, Kestrel; Guo, Qiang et al. (2009) Uridine insertion/deletion RNA editing in trypanosomatid mitochondria: In search of the editosome. RNA 15:1338-44
Li, Feng; Ge, Peng; Hui, Wong H et al. (2009) Structure of the core editing complex (L-complex) involved in uridine insertion/deletion RNA editing in trypanosomatid mitochondria. Proc Natl Acad Sci U S A 106:12306-10
Maslov, Dmitri A; Spremulli, Linda L; Sharma, Manjuli R et al. (2007) Proteomics and electron microscopic characterization of the unusual mitochondrial ribosome-related 45S complex in Leishmania tarentolae. Mol Biochem Parasitol 152:203-12