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Microbiology and Molecular Biology Reviews, March 2009, p. 36-61, Vol. 73, No. 1
1092-2172/09/$08.00+0     doi:10.1128/MMBR.00026-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Biochemical Features and Functional Implications of the RNA-Based T-Box Regulatory Mechanism

Ana Gutiérrez-Preciado,1 Tina M. Henkin,2 Frank J. Grundy,2 Charles Yanofsky,3 and Enrique Merino1*

Department of Molecular Microbiology, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México,1 Department of Microbiology and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210-1292,2 Department of Biological Sciences, Stanford University, Stanford, California 94305-50203

Summary: The T-box mechanism is a common regulatory strategy used for modulating the expression of genes of amino acid metabolism-related operons in gram-positive bacteria, especially members of the Firmicutes. T-box regulation is usually based on a transcription attenuation mechanism in which an interaction between a specific uncharged tRNA and the 5' region of the transcript stabilizes an antiterminator structure in preference to a terminator structure, thereby preventing transcription termination. Although single T-box regulatory elements are common, double or triple T-box arrangements are also observed, expanding the regulatory range of these elements. In the present study, we predict the functional implications of T-box regulation in genes encoding aminoacyl-tRNA synthetases, proteins of amino acid biosynthetic pathways, transporters, and regulatory proteins. We also consider the global impact of the use of this regulatory mechanism on cell physiology. Novel biochemical relationships between regulated genes and their corresponding metabolic pathways were revealed. Some of the genes identified, such as the quorum-sensing gene luxS, in members of the Lactobacillaceae were not previously predicted to be regulated by the T-box mechanism. Our analyses also predict an imbalance in tRNA sensing during the regulation of operons containing multiple aminoacyl-tRNA synthetase genes or biosynthetic genes involved in pathways common to more than one amino acid. Based on the distribution of T-box regulatory elements, we propose that this regulatory mechanism originated in a common ancestor of members of the Firmicutes, Chloroflexi, Deinococcus-Thermus group, and Actinobacteria and was transferred into the Deltaproteobacteria by horizontal gene transfer.

* Corresponding author. Mailing address: Instituto de Biotecnología, UNAM, Av. Universidad #2001, Col. Chamilpa, CP 62210 Cuernavaca, Morelos, México. Phone: 52 777 329 1634. Fax: 52 777 313 8673. E-mail: merino{at}ibt.unam.mx

Microbiology and Molecular Biology Reviews, March 2009, p. 36-61, Vol. 73, No. 1
1092-2172/09/$08.00+0     doi:10.1128/MMBR.00026-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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