Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 32, Pages 13132-13137Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1304795110
Keywords
asRNA; cobalamin; infection
Categories
Funding
- European Research Council [233348]
- Association Nationale de la Recherche (ANR) [BACNET 09-BLAN- 0024-02]
- ANR Investissement d'Avenir Programme [10-LABX-62]
- Fondation Le Roch
- Fondation Jeantet
- Umea University
- Swedish Research Council [K2011-56X-15144-08-6, 621-2012-2451]
- ERC Starting Grant [260764-RNAntibiotics]
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Riboswitches are ligand-binding elements located in 5' untranslated regions of messenger RNAs, which regulate expression of downstream genes. In Listeria monocytogenes, a vitamin B-12-binding (B-12) riboswitch was identified, not upstream of a gene but downstream, and antisense to the adjacent gene, pocR, suggesting it might regulate pocR in a nonclassical manner. In Salmonella enterica, PocR is a transcription factor that is activated by 1,2-propanediol, and subsequently activates expression of the pdu genes. The pdu genes mediate propanediol catabolism and are implicated in pathogenesis. As enzymes involved in propanediol catabolism require B-12 as a cofactor, we hypothesized that the Listeria B-12 riboswitch might be involved in pocR regulation. Here we demonstrate that the B-12 riboswitch is transcribed as part of a noncoding antisense RNA, herein named AspocR. In the presence of B-12, the riboswitch induces transcriptional termination, causing aspocR to be transcribed as a short transcript. In contrast, in the absence of B-12, aspocR is transcribed as a long antisense RNA, which inhibits pocR expression. Regulation by AspocR ensures that pocR, and consequently the pdu genes, are maximally expressed only when both propanediol and B-12 are present. Strikingly, AspocR can inhibit pocR expression in trans, suggesting it acts through a direct interaction with pocR mRNA. Together, this study demonstrates how pocR and the pdu genes can be regulated by B-12 in bacteria and extends the classical definition of riboswitches from elements governing solely the expression of mRNAs to a wider role in controlling transcription of noncoding RNAs.
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