The ultimate expression of the genetic makeup of a cell resides in the proteins of that cell. Although protein synthesis is a complex process requiring numerous proteins and nucleic acids, to a large extent the specificity is determined by the first step of the process - the activation and transfer of an amino acid to its respective transfer RNA. Although considerable information about aminoacyl-tRNA synthetases and TRNA has been obtained, relatively little is known about the control of protein synthesis that may be exercised at the level of aminoacyl-tRNA formation. Our long term goal is the elucidation of the pathways, enzymes and regulatory factors which determine the levels of tRNA and synthetases in cells, and their effect on the various cellular processes in which aminoacyl-tRNA participates. The studies we propose should provide needed information for this central area of macromolecular metabolism.
Specific aims for this project are: 1) to purify and determine the physiological role and possible regulation of newly-discovered ribonucleases thought to be involved in tRNA processing and turnover; 2) to evaluate the diversity and role of phosphorolytic nucleases in RNA metabolism; 3) to identify and study the functional domains of TRNA inucleotidyltransferase; 4) to determine the importance of the -C-C-A terminus for TRNA function in vivo; 5) to study the role of lipids and membranes in aminoacyl-tRNA synthetase structure and function and to determine whether aminoacyl-tRNA is channeled in vivo; 6) to ascertain the functional. significance, if any, of the low molecular weight free form of arginyl-tRNA synthetase. In view of the central role of proteins in all cell functions, and the importance aminoacyl-tRNA formation for the specificity of this process, an understanding of the mechanism and regulation of this step is of great importance . Elucidation of these aspects of protein synthesis in normal cells is a prerequisite to any understanding of abnormal situations which may occur under pathological conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM016317-25
Application #
3268894
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1974-09-01
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
25
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Dentistry
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
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
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; 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
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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