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Global Regulatory Functions of the Staphylococcus aureus Endoribonuclease III in Gene Expression

Please always quote using this URN: urn:nbn:de:bvb:20-opus-127219
  • RNA turnover plays an important role in both virulence and adaptation to stress in the Gram-positive human pathogen Staphylococcus aureus. However, the molecular players and mechanisms involved in these processes are poorly understood. Here, we explored the functions of S. aureus endoribonuclease III (RNase III), a member of the ubiquitous family of double-strand-specific endoribonucleases. To define genomic transcripts that are bound and processed by RNase III, we performed deep sequencing on cDNA libraries generated from RNAs that wereRNA turnover plays an important role in both virulence and adaptation to stress in the Gram-positive human pathogen Staphylococcus aureus. However, the molecular players and mechanisms involved in these processes are poorly understood. Here, we explored the functions of S. aureus endoribonuclease III (RNase III), a member of the ubiquitous family of double-strand-specific endoribonucleases. To define genomic transcripts that are bound and processed by RNase III, we performed deep sequencing on cDNA libraries generated from RNAs that were co-immunoprecipitated with wild-type RNase III or two different cleavage-defective mutant variants in vivo. Several newly identified RNase III targets were validated by independent experimental methods. We identified various classes of structured RNAs as RNase III substrates and demonstrated that this enzyme is involved in the maturation of rRNAs and tRNAs, regulates the turnover of mRNAs and non-coding RNAs, and autoregulates its synthesis by cleaving within the coding region of its own mRNA. Moreover, we identified a positive effect of RNase III on protein synthesis based on novel mechanisms. RNase III–mediated cleavage in the 5′ untranslated region (5′UTR) enhanced the stability and translation of cspA mRNA, which encodes the major cold-shock protein. Furthermore, RNase III cleaved overlapping 5′UTRs of divergently transcribed genes to generate leaderless mRNAs, which constitutes a novel way to co-regulate neighboring genes. In agreement with recent findings, low abundance antisense RNAs covering 44% of the annotated genes were captured by co-immunoprecipitation with RNase III mutant proteins. Thus, in addition to gene regulation, RNase III is associated with RNA quality control of pervasive transcription. Overall, this study illustrates the complexity of post-transcriptional regulation mediated by RNase III.show moreshow less

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Metadaten
Author: Efthimia Lioliou, Cynthia M. Sharma, Isabelle Caldelari, Anne-Catherine Helfer, Pierre Fechter, François Vandenesch, Jörg Vogel, Pascale Romby
URN:urn:nbn:de:bvb:20-opus-127219
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):PLoS Genetics
Year of Completion:2012
Volume:8
Issue:6
Pagenumber:e1002782
Source:PLoS Genetics 8(6): e1002782. doi:10.1371/journal.pgen.1002782
DOI:https://doi.org/10.1371/journal.pgen.1002782
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:RNA denaturation; RNA sequencing; RNA structure; RNA synthesis; antisense RNA; messenger RNA; ribonucleases; staphylococcus aureus
Release Date:2016/07/15
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung