The ultimate expression of the genetic makeup of a cell resides in its proteins. When and how much of a protein will be synthesized depends on RNA molecules, which not only direct the process, but also constitute the machinery which assembles the proteins from amino acids. Thus, understanding RNA metabolism is a prerequisite for elucidating gene expression in normal cells and for clarifying what has gone wrong under a variety of pathological conditions, many of which are manifested by abnormal gene expression. While considerable information has accumulated about the ribonucleases (RNases) essential to RNA metabolism, much remains to be learned about their complete number, about their physiological roles, about their mechanism of action, and whether and how they might be regulated. It is the long term goal of this project to define the enzymes, pathways and regulatory factors that constitute the totality of RNA metabolism in a single cell. As RNA metabolism is remarkably similar in all cells, our studies continue to be carried out using the model organism, Escherichia coli, for which a large amount of information is already available.
Our specific aims are: 1) Examination of the pathway of stable RNA degradation under conditions of stress, and comparison with that of RNA quality control;2) Analysis of the novel regulatory process determining RNase R levels in cells;3) Elucidation of the physiological roles of RNase BN and RNase D;4) Determination of the substrate specificity and mode of action of RNase BN;and 5) Identification of additional RNases participating in maturation of rRNA. To accomplish these aims we will use a combination of approaches involving biochemical, molecular biological, genetic, physiological and immunological procedures. We anticipate that the studies detailed in this proposal will provide important, new information on the enzymes, factors and processes that encompass RNA metabolism.

Public Health Relevance

Inasmuch as RNA metabolism is intimately involved in almost all aspects of cell function, knowledge of all facets of RNA metabolism is essential if we are to completely understand the details of gene expression in normal cells, of what may go wrong in many disease states, and if we are to be successful in correcting pathological processes caused by altered gene expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM016317-45
Application #
8474772
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Bender, Michael T
Project Start
1974-09-01
Project End
2015-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
45
Fiscal Year
2013
Total Cost
$503,322
Indirect Cost
$173,185
Name
University of Miami School of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Hossain, Sk Tofajjen; Deutscher, Murray P (2016) Helicase Activity Plays a Crucial Role for RNase R Function in Vivo and for RNA Metabolism. J Biol Chem 291:9438-43
Hossain, Sk Tofajjen; Malhotra, Arun; Deutscher, Murray P (2016) How RNase R Degrades Structured RNA: ROLE OF THE HELICASE ACTIVITY AND THE S1 DOMAIN. J Biol Chem 291:7877-87
Sulthana, Shaheen; Basturea, Georgeta N; Deutscher, Murray P (2016) Elucidation of pathways of ribosomal RNA degradation: an essential role for RNase E. RNA 22:1163-71
Chen, Hua; Dutta, Tanmay; Deutscher, Murray P (2016) Growth Phase-dependent Variation of RNase BN/Z Affects Small RNAs: REGULATION OF 6S RNA. J Biol Chem 291:26435-26442
Yuan, Fenghua; Dutta, Tanmay; Wang, Ling et al. (2015) Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-stranded RNA. J Biol Chem 290:13344-53
Liang, Wenxing; Rudd, Kenneth E; Deutscher, Murray P (2015) A role for REP sequences in regulating translation. Mol Cell 58:431-9
Hossain, Sk Tofajjen; Malhotra, Arun; Deutscher, Murray P (2015) The Helicase Activity of Ribonuclease R Is Essential for Efficient Nuclease Activity. J Biol Chem 290:15697-706
Liang, Wenxing; Deutscher, Murray P (2013) Ribosomes regulate the stability and action of the exoribonuclease RNase R. J Biol Chem 288:34791-8
Sulthana, Shaheen; Deutscher, Murray P (2013) Multiple exoribonucleases catalyze maturation of the 3' terminus of 16S ribosomal RNA (rRNA). J Biol Chem 288:12574-9
Dutta, Tanmay; Malhotra, Arun; Deutscher, Murray P (2013) How a CCA sequence protects mature tRNAs and tRNA precursors from action of the processing enzyme RNase BN/RNase Z. J Biol Chem 288:30636-44

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