NON-CODING RNA Sequestration by Riboswitches

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NON-CODING RNA Sequestration by riboswitches

Riboswitches are non-coding regula- 450-nucleotide ncRNA transcript In parallel to the findings in tory mRNA elements found in the (Rli55) was produced, whereas a L. monocytogenes, DebRoy et al. these studies 5ʹ untranslated regions of bacterial shorter 200-nucleotide transcript discovered a small regulatory RNA, extend the role transcripts. In response to metabolic was generated in the presence of EutX, that mediates eut expression ligands, riboswitches typically control these compounds. This finding sug- by sequestering EutV proteins in of riboswitches RNA expression by inducing con- gests that the vitamin B12-sensitive Enterococcus faecalis. This small as regulators formational changes in downstream riboswitch mediates transcriptional RNA contains an adenosyl cobala- of both ncRNA regions. Two new studies show termination of Rli55. Furthermore, mine (AdoCbl, the active form of and protein that riboswitches can also mediate they showed that eut gene expression vitamin B12)-sensitive riboswitch. gene expression by controlling the levels are negatively correlated with Binding of the cofactor AdoCbl to availability transcription of non-coding RNAs Rli55 expression. In particular, the riboswitch in the presence of (ncRNAs) and by regulating the mutant strains containing deletions ethanolamine prevents formation sequestration of specific proteins. of the Rli55 locus showed high of hairpin structures in EutX, which This regulation contains an addi- levels of eut gene expression, whereas are required for EutV binding. Thus, tional level of control, as it requires mutant strains that had a mutation in the presence of AdoCbl, EutX the presence of specific cofactors. in the riboswitch (and thus consti- cannot bind to and sequester EutV, Both studies investigated the tutively produced Rli55) had low eut leaving it free to activate expression ethanolamine utilization (eut) gene expression levels irrespective of of the eut genes. Conversely, in the pathway, which is widely conserved the presence or absence of vitamin absence of AdoCbl, EutX is able to across various pathogens. The upreg- B12 and ethanolamine. form these hairpin structures, and ulation of this pathway is frequently How does Rli55 regulate eut can therefore bind to and sequester associated with pathogenesis. gene expression? The researchers EutV, leading to downregulation of Mellin et al. focused on a vitamin identified ANTAR (AmiR and eut gene expression. B12-sensitive riboswitch in Listeria NasR transcriptional antiterminator Together, these studies extend the monocytogenes upstream of the eut regulator) elements within Rli55, role of riboswitches as regulators of locus. Using RNA sequencing and and showed that these elements both ncRNA and protein availability, quantitative real time PCR, they are necessary and sufficient to and provide further insights into showed that eut gene expression regulate the eut genes. Specifically, RNA regulation in bacteria, as well requires both the cofactor vitamin ANTAR elements are required for as new links between metabolite B12 and ethanolamine, which sug- Rli55 to act as a ‘sponge’, binding to sensing, RNA structure and protein gests that this vitamin B12-sensitive and sequestering the EutV protein, sequestration. Isabel Lokody riboswitch regulates eut gene expres- which is required for eut gene sion. To investigate this possibility, the expression. Interestingly, using ORIGINAL RESEARCH PAPERS Mellin, J. R. team examined the transcription of several L. monocytogenes mutants in et al. Sequestration of a two-component response regulator by a riboswitch-regulated noncoding the riboswitch locus using Northern a mouse infection model, Mellin and RNA. Science 345, 940–943 (2014) | DebRoy, S. blotting with a probe complementary co-workers showed that defects in et al. A riboswitch-containing sRNA controls gene to the riboswitch. In the absence of ethanolamine utilization attenuate expression by sequestration of a response regulator. Science 345, 937–940 (2014) vitamin B12 and ethanolamine, a virulence of this pathogen.

NATURE REVIEWS | GENETICS VOLUME 15 | OCTOBER 2014