ReviewTranscription termination control in bacteria
Introduction
Regulation of gene expression at the level of transcription termination, originally discovered as a key element of the bacteriophage λ developmental program, has emerged as an important mechanism for control of a variety of genetic systems. Two classes of transcription termination signals, both of which are active in the nascent transcript, have been identified in bacteria: intrinsic terminators, composed of a G+C-rich stem-loop followed by a series of U residues, and Rho-dependent terminators, whose activity relies on binding of the Rho protein to a rut (Rho utilization) site on the nascent transcript, followed by interaction with RNA polymerase (RNAP). Recent analyses of transcription, using elegant biochemical and structural biological approaches, have yielded new levels of understanding of the mechanisms of transcription elongation and termination (reviewed in 1••, 2••; see Severinov, this issue pp 118–125). This information continues to provide insight into the ways in which these processes can be controlled, through modulation of the activity of RNAP and through alterations in the structure of the nascent RNA. The possibility remains that important differences between Escherichia coli RNAP and the transcriptional machinery in other organisms may impact control mechanisms in interesting and unexpected ways. This review focuses on the basic themes of transcription termination control mechanisms found in bacteria (reviewed in [3]) with an emphasis on systems for which new information has recently been described.
Section snippets
Effects on transcriptional processivity
Transcription termination at both intrinsic and Rho-dependent terminators is dependent on pausing of RNAP at a specific site, followed by destabilization of the paused complex. Pausing is directed by sequence and structural elements, and the sensitivity of RNAP to these elements can be modulated in a variety of ways, including interaction of protein factors with RNAP to control pausing or escape from the paused state. Systems of this type were reviewed recently [4••].
Control of nascent transcript structure
A variety of systems have been reported in which transcription termination is controlled by modulation of the structure of the nascent transcript, often by formation of an alternate structure that competes with formation of the stem-loop of an intrinsic terminator located in the leader region of the transcript. Originally described for amino acid biosynthetic operons in E. coli and Salmonella, where the translation efficiency of a leader peptide coding region affects the relative positions of
New interfaces between transcription termination control and translation
As noted above, control of transcription termination via translation of a leader open reading frame represents a paradigm system for regulating the activity of an intrinsic terminator by controlling leader RNA structure. The E. coli tna operon reveals a novel variation on this theme, in which nascent peptide-dependent ribosome pausing blocks access of Rho to a leader region rut site, thereby controlling transcription termination and expression of the downstream tryptophanase gene [47]. Growth
Conclusions
A growing number of genetic systems in bacteria are regulated at the level of transcription termination. It is especially notable that analysis of organisms other than E. coli and its relatives has revealed novel variations on the paradigm systems. In particular, Gram-positive bacteria seem especially subject to utilization of systems of this type and application of a single mechanism (e.g. the T box or S box systems) to large groups of genes. Further analysis of new groups of organisms is
Acknowledgements
I thank many colleagues for valuable discussions and for providing information prior to publication. Work in my lab on transcription termination control is provided by the National Institutes of Health (GM47823).
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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