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The Trager Lectures
A Symposium to Honor a Lifetime of Contributions by Dr. William Trager to the Study of Malaria
Saturday, June 18, 2005 - Lillie Auditorium, 2:00 PM.
Uridine insertion/deletion RNA editing as a paradigm for site-specific modifications of RNA molecules
Larry Simpson, Ph.D., Principal Investigator, Howard Hughes Medical Institute and Professor, Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles
Lecture Abstract:
A sense of wonderment at the variety, complexity and beauty of natural phenomena is, I believe, the defining characteristic of our species. In my own case, the trypanosomatid protists caught my imagination many years ago entirely due to the insight of my Ph.D. mentor, Bill Trager, and never let go. Wonder after wonder emerged from the study of these creatures, with the most striking being uridine insertion/deletion RNA editing, which is a very successful but apparently unique evolutionary adaptation for gene regulation. In this talk I will address how this phenomenon evolved, why is it still maintained, and why is it restricted to trypanosomes? In addition I will review recent advances in our knowledge of the biochemistry and molecular mechanisms of this process. And finally I will discuss the biological significance of RNA modifications in general and attempt to provide a rationale for the trypanosome type of RNA editing being a paradigm for multiple other types of site-specific modifications of RNA molecules, including cytidine deamination in apoB mRNA, adenosine deamination in certain nervous system related mRNAs, sno-RNA mediated nucleotide modifications of ribosomal RNAs, and siRNA-mediated degradation of mRNAs in RNA interference. All represent non-encoded modifications of RNAs and the modifications are site-specific. Furthermore, site specificity is determined by the simple rules of base pairing of nucleic acids as exemplified by the guide RNA-mediated trypanosome editing.
Dr. Larry Simpson is a Professor of Molecular, Cell, and Developmental Biology and of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles, David Geffen School of Medicine and a Howard Hughes Medical Institute Investiator. He is a member of the Molecular Biology Institute and the Jonsson Cancer Institute at UCLA. Dr. Simpson received his B.A. degree in biology from Princeton University and his Ph.D. degree in molecular parasitology with William Trager at the Rockefeller University. His postdoctoral training was with Maurice Steinert at the Free University of Brussels. Dr. Simpson is a foreign member of the Brazilian Academy of Sciences. Dr. Simpson is interested in the mechanism of the uridine-insertion/deletion RNA editing that occurs in trypanosome mitochondria. He is also interested in the importation of transfer RNAs into the mitochondrion in these cells.
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