Messenger RNA turnover has long been recognized to play a key role in controlling gene expression in all organisms. The long-term goal of this research project is to understand the basic principles that govern mRNA degradation in bacterial cells. The immediate objectives are to elucidate the specificity and mechanism of 5'-end-dependent RNA degradation in Escherichia coli and Bacillus subtilis by investigating the proteins that are central to this regulatory pathway and the transcripts that they target. Achieving these objectives will require not only the use of standard molecular biological, biochemical, and genetic methods but also the development of new low- and high-throughput techniques for analyzing the 5' phosphorylation state of individual transcripts and for using genetic screening to identify pertinent clones and mutants. The knowledge gained from these studies will provide important insights into a fundamental aspect of gene regulation that can play a key role in bacterial pathogenesis.

Public Health Relevance

The proposed research will address the mechanisms by which messenger RNA is degraded in bacterial cells. The knowledge thereby acquired is expected to be of value in understanding the regulatory processes that govern bacterial pathogenesis and in maximizing bacterial production of medically useful proteins. In addition, the methods and concepts developed in the course of these studies are likely to be useful for elucidating how messenger RNA degradation helps to ensure proper levels of gene expression in healthy human cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM035769-27A1
Application #
8632148
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Bender, Michael T
Project Start
1986-01-01
Project End
2017-12-31
Budget Start
2014-01-15
Budget End
2014-12-31
Support Year
27
Fiscal Year
2014
Total Cost
$364,425
Indirect Cost
$149,425
Name
New York University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Vogel, Jörg; Gottesman, Susan; Belasco, Joel et al. (2014) Meeting report: Regulating with RNA in Bacteria 2013. RNA Biol 11:403-12
Hsieh, Ping-kun; Richards, Jamie; Liu, Quansheng et al. (2013) Specificity of RppH-dependent RNA degradation in Bacillus subtilis. Proc Natl Acad Sci U S A 110:8864-9
Richards, Jamie; Liu, Quansheng; Pellegrini, Olivier et al. (2011) An RNA pyrophosphohydrolase triggers 5'-exonucleolytic degradation of mRNA in Bacillus subtilis. Mol Cell 43:940-9
Richards, Jamie; Belasco, Joel G (2011) Ribonuclease J: how to lead a double life. Structure 19:1201-3
Yao, Shiyi; Richards, Jamie; Belasco, Joel G et al. (2011) Decay of a model mRNA in Bacillus subtilis by a combination of RNase J1 5' exonuclease and RNase Y endonuclease activities. J Bacteriol 193:6384-6
Belasco, Joel G (2010) All things must pass: contrasts and commonalities in eukaryotic and bacterial mRNA decay. Nat Rev Mol Cell Biol 11:467-78
Schuck, Alyssa; Diwa, Alexis; Belasco, Joel G (2009) RNase E autoregulates its synthesis in Escherichia coli by binding directly to a stem-loop in the rne 5'untranslated region. Mol Microbiol 72:470-8
Messing, Simon A J; Gabelli, Sandra B; Liu, Quansheng et al. (2009) Structure and biological function of the RNA pyrophosphohydrolase BdRppH from Bdellovibrio bacteriovorus. Structure 17:472-81
Celesnik, Helena; Deana, Atilio; Belasco, Joel G (2008) PABLO analysis of RNA 5'-phosphorylation state and 5'-end mapping. Methods Enzymol 447:83-98
Celesnik, Helena; Deana, Atilio; Belasco, Joel G (2007) Initiation of RNA decay in Escherichia coli by 5'pyrophosphate removal. Mol Cell 27:79-90

Showing the most recent 10 out of 33 publications