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 #
5R01GM016317-44
Application #
8334513
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
2012-06-01
Budget End
2013-05-31
Support Year
44
Fiscal Year
2012
Total Cost
$521,578
Indirect Cost
$179,467
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
Schmier, Brad J; Seetharaman, Jayaraman; Deutscher, Murray P et al. (2012) The structure and enzymatic properties of a novel RNase II family enzyme from Deinococcus radiodurans. J Mol Biol 415:547-59
Vincent, Helen A; Deutscher, Murray P (2009) Insights into how RNase R degrades structured RNA: analysis of the nuclease domain. J Mol Biol 387:570-83
Kyriacou, Sophia V; Deutscher, Murray P (2008) An important role for the multienzyme aminoacyl-tRNA synthetase complex in mammalian translation and cell growth. Mol Cell 29:419-27