Novel regulation from novel interactions: Identification of an RNA sponge that controls the levels, processing and efficacy of the RoxS riboregulator of central metabolism inBacillus subtilis

Autor: Juan Ramon Hernandez-Fernaud, Gergana Kostova, Adam Callan-Sidat, Josie Mckeown, Sylvain Durand, Chrystala Constantinidou, Stephen Li, Emma L. Denham, Mohammad Tauqeer Alam, Ciarán Condon, Andrew D. Millard
Přispěvatelé: Expression Génétique Microbienne (EGM (UMR_8261 / FRE_3630)), Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie physico-chimique (IBPC (FR_550))
Rok vydání: 2019
Předmět:
DOI: 10.1101/814905
Popis: Small RNAs (sRNAs) are a taxonomically-restricted but transcriptomically-abundant class of post-transcriptional regulators. While potentially of importance, we know the function of few. This is in no small part because we lack global-scale methodology enabling target identification, this being especially acute in species without known RNA meeting point proteins (e.g. Hfq). We apply a combination of psoralen RNA cross-linking and Illumina-sequencing to identify RNA-RNA interacting pairsin vivoinBacillus subtilis, resolving previously well-described interactants. Although sRNA-sRNA pairings are rare (compared with sRNA/mRNA), we identify a robust example involving the unusually conserved sRNA (RoxS/RsaE) and an unstudied sRNA that we term Regulator of small RNA A (RosA). This interaction is found in independent samples across multiple conditions. Given the possibility of a novel associated regulatory mechanism, and the rarity of well-characterised bacterial sRNA-sRNA interactions, we mechanistically dissect RosA and its interactants. RosA we show to be a sponge RNA, the first to be described in a Gram-positive bacterium. RosA interacts with at least two sRNAs, RoxS and FsrA. Unexpectedly, it acts differently on each. As expected of a sponge RNA, FsrA is sequestered by RosA. The RosA/RoxS interaction is more complex affecting not only the level of RoxS but also its processing and efficacy. Importantly, RosA provides the condition-dependent intermediary between CcpA, the key regulator of carbon metabolism, and RoxS. This not only provides evidence for a novel, and functionally important, regulatory mechanism, but in addition, provides the missing link between transcriptional and post-transcriptional regulation of central metabolism.
Databáze: OpenAIRE