The Bacillus subtilis tyrS gene is a member of a group of aminoacyl-tRNA synthetase and amino acid biosynthesis genes, designated the T box family, which are regulated by a unique transcription antitermination system. Expression of these genes is dependent on interaction of the leader region of the transcript with a specific uncharged tRNA. This interaction promotes formation of an antiterminator structure, preventing premature termination of transcription. At least 27 genes have been identified as members of this family in Gram-positive bacteria, including several pathogenic species. The T box mechanism has not yet been found in Gram negative bacteria. The tyrS gene is the best characterized member of this group. The specificity of the leader RNA-tRNA interaction is dependent on pairing of the anticodon of the tRNA with a single codon, the """"""""specifier sequence,"""""""" in the leader, and on pairing of the acceptor end of the tRNA with a portion of the antiterminator. These pairings are necessary for a successful interaction, but other features of the tRNA and the leader are likely to be important. One goal of this study is to further investigate this interaction, using both genetic and biochemical techniques. A number of conserved leader region elements are essential for antitermination. A second major goal is examination of the molecular role of these elements. While the tRNA-leader interaction is required for antitermination, it is not clear that this interaction is sufficient. A third major goal of this study is to identify any additional required factors by mutational analyses, and by reconstitution of the antitermination system in vitro and in a heterologous host. Overall these studies are designed to elucidate the molecular mechanism of T box gene antitermination.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047823-08
Application #
6342853
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Rhoades, Marcus M
Project Start
1993-12-01
Project End
2002-08-31
Budget Start
2001-01-01
Budget End
2002-08-31
Support Year
8
Fiscal Year
2001
Total Cost
$255,697
Indirect Cost
Name
Ohio State University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Sherwood, Anna V; Frandsen, Jane K; Grundy, Frank J et al. (2018) New tRNA contacts facilitate ligand binding in a Mycobacterium smegmatis T box riboswitch. Proc Natl Acad Sci U S A 115:3894-3899
Kreuzer, Kiel D; Henkin, Tina M (2018) The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation. Microbiol Spectr 6:
Sherwood, Anna V; Henkin, Tina M (2016) Riboswitch-Mediated Gene Regulation: Novel RNA Architectures Dictate Gene Expression Responses. Annu Rev Microbiol 70:361-74
Caserta, Enrico; Liu, Liang-Chun; Grundy, Frank J et al. (2015) Codon-Anticodon Recognition in the Bacillus subtilis glyQS T Box Riboswitch: RNA-DEPENDENT CODON SELECTION OUTSIDE THE RIBOSOME. J Biol Chem 290:23336-47
Liu, Liang-Chun; Grundy, Frank J; Henkin, Tina M (2015) Non-Conserved Residues in Clostridium acetobutylicum tRNA(Ala) Contribute to tRNA Tuning for Efficient Antitermination of the alaS T Box Riboswitch. Life (Basel) 5:1567-82
Sherwood, Anna V; Grundy, Frank J; Henkin, Tina M (2015) T box riboswitches in Actinobacteria: translational regulation via novel tRNA interactions. Proc Natl Acad Sci U S A 112:1113-8
Williams-Wagner, Rebecca N; Grundy, Frank J; Raina, Medha et al. (2015) The Bacillus subtilis tyrZ gene encodes a highly selective tyrosyl-tRNA synthetase and is regulated by a MarR regulator and T box riboswitch. J Bacteriol 197:1624-31
Henkin, Tina M (2014) The T box riboswitch: A novel regulatory RNA that utilizes tRNA as its ligand. Biochim Biophys Acta 1839:959-963
Grigg, Jason C; Chen, Yujie; Grundy, Frank J et al. (2013) T box RNA decodes both the information content and geometry of tRNA to affect gene expression. Proc Natl Acad Sci U S A 110:7240-5
Caserta, Enrico; Haemig, Heather A H; Manias, Dawn A et al. (2012) In vivo and in vitro analyses of regulation of the pheromone-responsive prgQ promoter by the PrgX pheromone receptor protein. J Bacteriol 194:3386-94

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