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 number, their physiological roles, 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 processes 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: 1a) Examination of growth phase regulation of RNase BN and RNase D; 1b) Use the information from Aim 1a to determine how changes in the levels of RNases BN and D regulate small RNAs; 2) Elucidation of the pathways and RNases involved in ribosomal RNA degradation; 3) Determination of the RNases and factors responsible for maturation of ribosomal RNA; and 4) Analysis of the intrinsic helicase activity of RNase R and its importance to the mechanism of action and in vivo functions of RNase R. 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.
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.
| Sulthana, Shaheen; Quesada, Ernesto; Deutscher, Murray P (2017) RNase II regulates RNase PH and is essential for cell survival during starvation and stationary phase. RNA 23:1456-1464 |
| 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 |
| Liang, Wenxing; Deutscher, Murray P (2016) REP sequences: Mediators of the environmental stress response? RNA Biol 13:152-6 |
| Song, Limin; Wang, Guangyuan; Malhotra, Arun et al. (2016) Reversible acetylation on Lys501 regulates the activity of RNase II. Nucleic Acids Res 44:1979-88 |
| 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 |
| 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 |
| 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 |
| 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 |
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