This is a continuation of a multi-faceted project whose overall objective has been to understand the processes involved in gene expression in molecular terms. During its first five years, the project has been concerned with elucidating the structural characteristics of transcriptional and translational control signals and understanding how particular alterations in these signals can affect gene expression. At this time, the project's focus has shifted to an aspect of gene expression that previously has received relatively little attention--namely, the role of mRNA stability in genetic control and the mechanisms by which mRNA turnover occurs.
The specific aims for the next period of work are: (1) To identify the structural signals that determine transcript stability or instability, (2) To elucidate the nucleolytic processes involved in mRNA degradation, (3) to understand the mechanisms by which biological processes such as rate of cell growth and translation of mRNA by ribosomes affect mRNA stability, and (4) To elucidate the mechanisms involved in the regulation of gene expression at the level of decay and processing of the rxcA transcript of R. capsulata. Initially, studies will be carried out in the prokaryotic organisms, E. coli and Rhodopseudomonas capsulata; at a later stage in the project, the role of mRNA stability in modulating gene expression within eukaryotic cells will be investigated.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Stanford University
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Claverie-Martin, F; Wang, M; Cohen, S N (1997) ARD-1 cDNA from human cells encodes a site-specific single-strand endoribonuclease that functionally resembles Escherichia coli RNase E. J Biol Chem 272:13823-8
McDowall, K J; Cohen, S N (1996) The N-terminal domain of the rne gene product has RNase E activity and is non-overlapping with the arginine-rich RNA-binding site. J Mol Biol 255:349-55
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Xu, F; Lin-Chao, S; Cohen, S N (1993) The Escherichia coli pcnB gene promotes adenylylation of antisense RNAI of ColE1-type plasmids in vivo and degradation of RNAI decay intermediates. Proc Natl Acad Sci U S A 90:6756-60
Klug, G; Cohen, S N (1991) Effects of translation on degradation of mRNA segments transcribed from the polycistronic puf operon of Rhodobacter capsulatus. J Bacteriol 173:1478-84
Lin-Chao, S; Cohen, S N (1991) The rate of processing and degradation of antisense RNAI regulates the replication of ColE1-type plasmids in vivo. Cell 65:1233-42
Klug, G; Cohen, S N (1990) Combined actions of multiple hairpin loop structures and sites of rate-limiting endonucleolytic cleavage determine differential degradation rates of individual segments within polycistronic puf operon mRNA. J Bacteriol 172:5140-6

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