Control of transcription termination in bacteria by RNA-binding proteins that modulate RNA structures

During the past few years, our knowledge of gene regulation by RNA-binding proteins has greatly increased. RNA-binding proteins are involved in processes such as protection of RNAs from RNase degradation, prevention of ribosome binding to mRNA, control of formation of secondary structures of the mRNA that pen-nit or prevent translation initiation, and termination/antitermination of transcription in response to external signals. Modulation of transcription termination by RNA-binding proteins involves the formation of alternative structures. One of the structures can act as a transcriptional terminator, while adoption of the alternative structure prevents formation of the terminator and does thus result in transcript elongation. Which of the two structures prevails under a given condition depends on two factors: the intrinsic stability of the alternative structures and the stabilization of one of both by an RNA-binding regulatory protein. Binding of a protein to the nascent mRNA may result in transcript elongation, as is the case for cold-shock proteins or in several catabolic operons. The RNA-binding ability of the RNA-binding proteins is modulated by direct interaction with the inducer, by protein-protein interactions with sensor proteins or by protein phosphorylation. In contrast, in the pyrimidine or tryptophan biosynthetic operons of Bacillus subtilis, the transcriptional terminators are stabilized by RNA-binding proteins resulting in the absence of expression of these operons. most bacterial mRNAs, this provides an efficient way to control the synthesis of any given protein. Most frequently, transcription initiation is tightly regulated by alternative sigma factors, repressors, or activators. In several operons, however, transcription is constitutively initiated, but elongation can only proceed under specific conditions. Regulated transcription elongation can be brought about by different mechanisms: (1) by proteins that bind to RNA polymerase and allow the elongation beyond termination signals, or (2) by the formation of alternative mRNA structures that result in either transcription termination or elongation. The formation of alternative RNA structures can in turn be modulated by tRNAs that bind to the mRNAs or by mRNA-binding proteins that support the formation of structures effective in termination or elongation (antitermination). The mechanism of transcriptional termination/antitermination controlled by RNA-binding proteins will be the subject of this review. Due to space limitations, only recent work shall be reviewed here. Several earlier reviews have dealt with aspects of this subject (Henkin 2000; Rutberg 1997).