Peter Sarnow

Sarnow, Peter, Associate Professor Microbiology and Immunology Stanford University School of Medicine, Fairchild D307, Stanford, CA 94305-5124 Tel: (650) 498-7076 Fax: (650) 498-7147

Email: psarnow@leland.stanford.edu

A unique feature of all cytoplasmic eukaryotic mRNA molecules is the presence of a m7GpppN "cap" structure at the 5' end of the RNAs. Cap-dependent translational initiation involves a concerted interaction of the cap-binding protein complex elF-4F with eht cap structure. It is thought that elF-4F mediates the binding of the 40S ribosomal subunits at or near the 5' end of the mRNA. Subsequently, the 40S ribosomal subunits are predicted to scan the mRNA in a 5' to 3' direction until the first AUG codon is encountered as start site for protein synthesis. This model is known as the "scanning mechanism" for translation initiantion. However, certain mRNAs, notably, encoding pro-oncogenes and regulatory genes, contain long 5'noncoding regions (5'NCRs) with multiple AUG codons. Thus, the translation initiation rate of these mRNAs is predicted to be quite low according to mthe scanning model; alternatively, other translation initiation mechanisms, may operate to ensure efficient translation.

Much of our work has been focussing on the mechanism and prevalence of internal ribosome binding, a unique mechanism of translational initiation used by certain cellular and viral mRNAs containing long 5'NCRs. Specifically, we are addresssing the following questions: WHich cellular and viral mRNAs can be translated by internal ribosome binding? What are the celullar gene products that mediate internal ribosome binding? Is internal initiation regulated in the cell? What is the molecular basis for designating a given AUG codon as start site codon?

In addition, we have been studying the mechanism by which piconaviruses, positive-stranded RNA viruses, amplify their genomic RNAs in infected cells. Manipulation of an infectious poliovirus cDNA has revealed the presence of a pseudoknot structure in the 3'NCR of the viral genome. We are currently invesitgating the role of this RNA structure and associated RNA binding proteins in the selective amplification of viral RNA molecules in infected cells.

Macejak, D.G. and Sarnow, P. 1991. Internal initiation of translation mediated by the 5' leader of a cellular mRNA. Nature 353:90-94
OH, S-K., Scott, M.P. and Sarnow, P. 1992. Homeotic gene Antennapedia mRNA contains 5' noncoding sequences that confer translational initiation by internal ribosome binding. Genes and Development 6:1643-1653
Hambidge, S.J. and Sarnow, P. 1992. Translational enhancement of the poliovirus 5' noncoding region mediated by virus-encoded polypeptide 2A. Proc. Natl. Acad. Sci. USA 89:10272-10276
Chen, C. and Sarnow, P. 1995. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268: 415-417.
McBratney, S. and Sarnow, P. 1996 Evidence for the involvement of trans-acting factors in the selection of the AUG start codon during eukaryotic translational initiation. Mol. Cell. Bio. 16:3523-3534.

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