These investigations will focus on elucidating the mechanisms of messenger RNA degradation in prokaryotes and on identifying the structural features of bacterial transcripts that determine their stabilities. In particular, the decay of three mRNA species will be examined: the monocistronic ompA and bla messages of the enteric bacterium Escherichia coli and the polycistronic rxcA transcript of the photosynthetic bacterium Rhodopseudomonas capsulata. The experimental approach to be employed will involve creating defined mutations and fusions of these three genes in vitro, introducing these altered genetic constructs into appropriate bacterial hosts, and analyzing the decay of the resulting mRNA transcripts. The results of these studies should enhance our knowledge of a fundamental but much neglected aspect of gene expression that is poorly understood. This knowledge should ultimately be of value both to our understanding of a biological regulatory process that may be involved in human disease (e.g., Alzheimer's disease, thalassemia, cancer) and to efforts to improve yields of medically and commercially useful proteins produced in bacteria through recombinant DNA technology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035769-08
Application #
3288972
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1986-01-01
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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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