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The Ohio State University
Faculty Bios
Tina M. Henkin

Tina M. Henkin

henkin.3@osu.edu

Professor,
Ph.D., University of Wisconsin, 1984.

Transcription termination control in Gram-positive bacteria; RNA structure/function, RNA sensors.

The main area of interest in our laboratory is the analysis of the mechanisms through which cells sense changes in their environment and transmit that information to the level of gene expression. We use the Gram-positive bacterium Bacillus subtilis as a model system, and we focus on genes involved in protein synthesis and amino acid metabolism.

Transcription antitermination - nascent RNAs can sense uncharged tRNA:

Characterization of the B. subtilis tyrS gene, encoding tyrosyl-tRNA synthetase, revealed a novel mechanism of gene regulation at the level of transcription antitermination. The tyrS gene is a member of a large family of aminoacyl-tRNA synthetase and amino acid biosynthesis genes in Gram-positive bacteria that are regulated by a common mechanism. Each gene in this family responds individually to limitation for the appropriate amino acid. Amino acid limitation is monitored via interaction of the mRNA leader region of the gene with the cognate uncharged tRNA. This interaction is directed by pairing of the anticodon of the tRNA with a single codon, designated the "specifier sequence," in the mRNA leader. We have now demonstrateed that the mRNA-tRNA interaction occurs in the absence of translation, and that antitermination can occur in a purified transcription system with no additional cellular factors, indicating that the leader RNA is sufficient for specific recognition of the cognate tRNA. We are currently investigating the molecular details of the leader RNA-tRNA interaction, and the structural shifts in both RNA partners that occur upon binding.

 

Transcription antitermination - nascent RNAs can sense small molecules:

Analysis of genes involved in methionine metabolism revealed a second global transcription antitermination system, dedicated to genes in this pathway. Like the T box system, the S box system is also widely used in Gram-positive organisms. Genes regulated by this mechanism contain highly conserved sequence and structural elements in their mRNA leader regions, and expression is induced by starvation for methionine. We have now shown that the molecular effector for this system is S -adenosylmethionine, which binds directly to the leader RNA and modululates its structure to promote transcription termination. We have also shown that lysine biosynthesis genes are regulated by a similar mechanism, with specific leader RNA binding of lysine. Current work is focusing on the molecular mechanisms of effector recognition and RNA rearrangement in response to effector binding.


Recent Publications

 

Henkin, T. M. and C. Yanofsky. 2002. Regulation by transcription attenuation in bacteria: How RNA provides instructions for transcription termination/antitermination decisions. BioEssays 24: 700-707.

 

Grundy, F. J., W. C. Winkler and T. M. Henkin. 2002. tRNA-mediated transcription antitermination in vitro: Codon-anticodon pairing independent of the ribosome. Proc. Natl. Acad. Sci. USA 99: 11121-11126.

 

Gerdeman, M. S., T. M. Henkin and J. V. Hines. 2003. Solution structure of the B. subtilis T box antiterminator RNA: Seven-nucleotide bulge characterized by stacking and flexibility. J. Mol. Biol. 326: 189-201.

 

McDaniel, B. A. M., F. J. Grundy, I. Artsimovitch and T. M. Henkin. 2003. Transcription termination control of the S box system: direct measurement of S -adenosylmethionine by the leader RNA. Proc. Natl. Acad. Sci. USA. 100: 3083-3088.

 

Yousef, M. R., F. J. Grundy and T. M. Henkin. 2003. tRNA requirements for glyQS antitermination:  A new twist on tRNA.  RNA 9: 1148-1156.

 

Grundy, F. J., S. C. Lehman and T. M. Henkin. 2003. The L box regulon:  Lysine sensing by leader RNAs of bacterial lysine biosynthesis genes. Proc. Natl. Acad. Sci. USA 100: 12057-12062.

 

Grundy, F. J. and T. M. Henkin. 2004. Regulation of gene expression by effectors that bind to RNA. Curr. Opin. Microbiol. 7: 126-131.

Ito, M., Hicks, D.B., Henkin, T.M., Guffanti, A.A., Powers, B., Zvi, L., Uematsu, K. and Krulwich, T.A. 2004. MotPS is the stator-force generator for motility of alkaliphilic Bacillus and its homologue is a second functional Mot in Bacillus subtilis . Mol. Microbiol. 53:1035-1049.

 

Grundy, F. J. and T. M. Henkin. 2004. Kinetic analysis of tRNA-directed transcription antitermination of the Bacillus subtilis glyQS gene in vitro. J. Bacteriol. 186: 5392-5399.

Grundy, F. J., M. R. Yousef and T. M. Henkin. 2005. Monitoring uncharged tRNA during transcription of the Bacillus subtilis glyQS gene. J. Mol. Biol. 346: 73-81.

Yousef, M. R., F. J. Grundy and T. M. Henkin. 2005. Structural transitions induced by the interaction between tRNAGly and the Bacillus subtilis glyQS T box leader RNA. J. Mol. Biol. 349:273-287.

McDaniel, B. A., F. J. Grundy and T. M. Henkin. 2005. A tertiary structural element in S box leader RNAs is required for SAM-directed transcription termination. Mol. Microbiol. 57:1008-1021.

Fuchs, R.T., Grundy, F.J. and Henkin, T. M. 2006. The SMK box is a new SAM binding RNA element that regulates translation of bacterial SAM synthetase genes. Nature Struct. Mol. Biol. 13:226-233.

Gardner, J.G., Grundy, F.J., Henkin, T. M. and Escalante-Semerena, J.C. 2006. Control of acetyl-CoA synthetase (AcsA) activity by acetylation/deacetylation without NAD+ involvement in Bacillus subtilis. J. Bacteriol. 188:5460-5468.

Grundy, F.J. and Henkin, T. M. 2006. From ribosome to riboswitch: control of gene expression in bacteria by RNA structural rearrangements. Crit. Rev. Biochem. Mol. Biol. 41:329-338.

McDaniel, B.A.M., Grundy, F.J., Kurlekar, V., Tomsic, J. and Henkin, T. M. 2006. Identification of a mutation in the Bacillus subtilis SAM synthetase gene that results in derepression of S box gene expression. J. Bacteriol. 188:3674-3681.

Nelson, A., Henkin, T. M. and Agris. P.F. 2006. tRNA regulation of gene expression: interaction of an mRNA 5’-UTR with a regulatory tRNA. RNA 12:1254-1261.

Terahara, N., Fujisawa, M., Powers, B., Henkin, T. M., Krulwich, T.A. and Ito, M. 2006. An intergenic stem-loop mutation in the Bacillus subtilis ccpA-motPS operon increases motPS transcription and the MotPS contribution to motility. J. Bacteriol. 188:2701-2705.

Young, R., Henkin, T. M. and Turnbough, C.L., Jr. 2006. The Phage Meeting: classical venue, new momentum. J. Bacteriol. 188:4597-4600.

Henkin, T. M. and F. J. Grundy. 2007. Sensing metabolic signals with nascent RNA transcripts: The T box and S box riboswitches as paradigms. Cold Spring Harbor Symp. Quant. Biol., Regulatory RNAs. 71:231-237.

Fuchs, R. T., F. J. Grundy and T. M. Henkin. 2007. S-adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the SMK box riboswitch RNA. Proc. Natl. Acad. Sci. USA 104:4876-4880.


Department of Microbiology; The Ohio State University; 376 Bioscience Building; 484 West 12th Ave.; Columbus, Ohio USA; 43210-1292; Phone: 614-292-2301; Fax: 614-292-8120
Riffe Research Center

 

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Department of Microbiology
The Ohio State University
376 Biological Sciences Building
484 West 12th Ave.
Columbus, Ohio USA 43210-1292
Phone: 614-292-2301
Fax: 614-292-8120

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