A riboswitch-containing sRNA controls gene expression by sequestration of a response regulator

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Science  22 Aug 2014:
Vol. 345, Issue 6199, pp. 937-940
DOI: 10.1126/science.1255091

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A dual-action RNA switch for expression

Riboswitches are short segments of RNA that bind small molecules and switch between two different conformations, thereby regulating gene expression (see the Perspective by Chen and Gottesman). DebRoy et al. and Mellin et al. find a new class of riboswitches—in two different species of bacteria—that are both part of and regulate the production of a noncoding RNA. Each riboswitch ensures that a particular metabolic pathway is only activated in the presence of an essential small-molecule cofactor. In the absence of the cofactor, the full-length non-coding RNA is made and binds a regulator protein, preventing the regulator protein from inappropriately activating the metabolic pathway.

Science, this issue p. 937 and p. 940; see also p. 876


The ethanolamine utilization (eut) locus of Enterococcus faecalis, containing at least 19 genes distributed over four polycistronic messenger RNAs, appears to be regulated by a single adenosyl cobalamine (AdoCbl)–responsive riboswitch. We report that the AdoCbl-binding riboswitch is part of a small, trans-acting RNA, EutX, which additionally contains a dual-hairpin substrate for the RNA binding–response regulator, EutV. In the absence of AdoCbl, EutX uses this structure to sequester EutV. EutV is known to regulate the eut messenger RNAs by binding dual-hairpin structures that overlap terminators and thus prevent transcription termination. In the presence of AdoCbl, EutV cannot bind to EutX and, instead, causes transcriptional read through of multiple eut genes. This work introduces riboswitch-mediated control of protein sequestration as a posttranscriptional mechanism to coordinately regulate gene expression.

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