Until recently, the ability to polyadenylate RNA has been widely viewed as a special property of eukaryotic cells, where polyadenylation has an important role in generating functional messenger RNA and regulating its decay. Recent work has shown that polyadenylation of RNA has important biological effects in prokaryotes as well. The long term goal of this multifaceted project is to understand the genetics and biochemistry of polyadenylation in prokaryotes and to elucidate its biological function(s).
Its specific aims are to: 1) define the structural features of RNAs that determine their susceptibility to polyadenylation, 2) identify and characterize the genes and enzymes that mediate the specificity of adenylation and its effects on RNA decay, and 3) elucidate the effects of polyadenylation on gene expression, and particularly on the translation of messenger RNA. These investigations will use genetic and biochemical approaches, including oligonucleotide-directed mutagenesis to identify signals that trigger polyadenylation, in vivo enzymatic assays and novel genetic approaches to identify and functionally characterize bacterial enzymes and genes that govern polyadenylation and its effects, and mutational and biochemical analyses of the biological consequences of polyadenylation. The work will provide important basic knowledge about factors that affect microbial evolution and gene expression, and consequently the growth and development of microbes that produce human disease. Such an understanding is likely to also yield information of practical value for the manipulation of biological processes affected by RNA, including the production of medically important gene products in bacterial cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054158-04
Application #
6019144
Study Section
Molecular Biology Study Section (MBY)
Program Officer
Rhoades, Marcus M
Project Start
1996-07-01
Project End
2003-03-31
Budget Start
1999-07-01
Budget End
2003-03-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Tamura, Masaru; Moore, Christopher J; Cohen, Stanley N (2013) Nutrient dependence of RNase E essentiality in Escherichia coli. J Bacteriol 195:1133-41
Manasherob, Robert; Miller, Christine; Kim, Kwang-sun et al. (2012) Ribonuclease E modulation of the bacterial SOS response. PLoS One 7:e38426
Tamura, Masaru; Kers, Johan A; Cohen, Stanley N (2012) Second-site suppression of RNase E essentiality by mutation of the deaD RNA helicase in Escherichia coli. J Bacteriol 194:1919-26
Go, Hayoung; Moore, Christopher J; Lee, Minho et al. (2011) Upregulation of RNase E activity by mutation of a site that uncompetitively interferes with RNA binding. RNA Biol 8:1022-34
Xu, Weijing; Huang, Jianqiang; Lin, Richard et al. (2010) Regulation of morphological differentiation in S. coelicolor by RNase III (AbsB) cleavage of mRNA encoding the AdpA transcription factor. Mol Microbiol 75:781-91
Xu, Weijing; Huang, Jianqiang; Cohen, Stanley N (2008) Autoregulation of AbsB (RNase III) expression in Streptomyces coelicolor by endoribonucleolytic cleavage of absB operon transcripts. J Bacteriol 190:5526-30
Kim, Kwang-sun; Manasherob, Robert; Cohen, Stanley N (2008) YmdB: a stress-responsive ribonuclease-binding regulator of E. coli RNase III activity. Genes Dev 22:3497-508
Tamura, Masaru; Lee, Kangseok; Miller, Christine A et al. (2006) RNase E maintenance of proper FtsZ/FtsA ratio required for nonfilamentous growth of Escherichia coli cells but not for colony-forming ability. J Bacteriol 188:5145-52
Gao, Junjun; Lee, Kangseok; Zhao, Meng et al. (2006) Differential modulation of E. coli mRNA abundance by inhibitory proteins that alter the composition of the degradosome. Mol Microbiol 61:394-406
Caruthers, Jonathan M; Feng, Yanan; McKay, David B et al. (2006) Retention of core catalytic functions by a conserved minimal ribonuclease E peptide that lacks the domain required for tetramer formation. J Biol Chem 281:27046-51

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