Sequestration of a two-component response regulator by a riboswitch-regulated noncoding RNA

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Science  22 Aug 2014:
Vol. 345, Issue 6199, pp. 940-943
DOI: 10.1126/science.1255083

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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


Riboswitches are ligand-binding elements contained within the 5ʹ untranslated regions of bacterial transcripts, which generally regulate expression of downstream open reading frames. Here, we show that in Listeria monocytogenes, a riboswitch that binds vitamin B12 controls expression of a noncoding regulatory RNA, Rli55. Rli55, in turn, controls expression of the eut genes, whose products enable ethanolamine utilization and require B12 as a cofactor. Defects in ethanolamine utilization, or in its regulation by Rli55, significantly attenuate Listeria virulence in mice. Rli55 functions by sequestering the two-component response regulator EutV by means of a EutV-binding site contained within the RNA. Thus, Rli55 is a riboswitch-regulated member of the small group of regulatory RNAs that function by sequestering a protein and reveals a distinctive mechanism of signal integration in bacterial gene regulation.

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