Program Director/Principal Investigator (Last, First, Middle): Belasco, Joel G. Description: Project Summary and Relevance Project Summary These investigations will focus on using molecular biological, biochemical, and genetic methods to elucidate how messenger RNA is degraded in bacteria. Particular attention will be devoted to RppH, a recently discovered RNA pyrophosphohydrolase that triggers the degradation of primary transcripts in E. coli by a previously unrecognized mechanism: the rate-determining conversion of the 5'-terminal triphosphate to a monophosphate. First, the features of RNAs that determine their susceptibility to decay by this mechanism will be identified. In addition, the characteristics of RppH that are important for its activity and the cellular factors that may influence such 5'-end- dependent RNA degradation will be examined. Finally, the contribution of this pathway to mRNA decay in other bacterial species will be explored. The results of these studies will provide important insights into a fundamental aspect of gene regulation that presently is poorly understood. This knowledge should be of value in clarifying a biological regulatory mechanism that can play a key role in bacterial pathogenesis.

Public Health Relevance

Belasco, Joel G. Relevance The proposed research will address the mechanism of bacterial messenger RNA degradation, a basic biological process important for controlling gene expression in all living organisms. The knowledge thereby acquired should be of value in maximizing bacterial production of medically useful proteins and in elucidating a regulatory mechanism that can influence bacterial pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035769-26
Application #
8247038
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Bender, Michael T
Project Start
1986-01-01
Project End
2014-01-14
Budget Start
2012-04-01
Budget End
2014-01-14
Support Year
26
Fiscal Year
2012
Total Cost
$353,020
Indirect Cost
$144,749
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
Richards, Jamie; Belasco, Joel G (2016) Distinct Requirements for 5'-Monophosphate-assisted RNA Cleavage by Escherichia coli RNase E and RNase G. J Biol Chem 291:5038-48
Foley, Patricia L; Hsieh, Ping-kun; Luciano, Daniel J et al. (2015) Specificity and evolutionary conservation of the Escherichia coli RNA pyrophosphohydrolase RppH. J Biol Chem 290:9478-86
Belasco, Joel G (2015) Way to go, RNA. RNA 21:565-6
Luciano, Daniel J; Belasco, Joel G (2015) NAD in RNA: unconventional headgear. Trends Biochem Sci 40:245-7
Schmidt, Skye A; Foley, Patricia L; Jeong, Dong-Hoon et al. (2015) Identification of SMG6 cleavage sites and a preferred RNA cleavage motif by global analysis of endogenous NMD targets in human cells. Nucleic Acids Res 43:309-23
Hui, Monica P; Foley, Patricia L; Belasco, Joel G (2014) Messenger RNA degradation in bacterial cells. Annu Rev Genet 48:537-59
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
Luciano, Daniel J; Hui, Monica P; Deana, Atilio et al. (2012) Differential control of the rate of 5'-end-dependent mRNA degradation in Escherichia coli. J Bacteriol 194:6233-9
Richards, Jamie; Luciano, Daniel J; Belasco, Joel G (2012) Influence of translation on RppH-dependent mRNA degradation in Escherichia coli. Mol Microbiol 86:1063-72

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