Contributors: Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038); Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Institut de Biologie Intégrative de la Cellule (I2BC); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS); Center for Agricultural Water Research in China; China Agricultural University (CAU); ARN régulateurs bactériens et médecine (BRM); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ); CNRS/Universite Paris-Saclay; INSERM / Universite Rennes 1; 'Agence Nationale de la Recherche' (ANR) [ANR-15-CE12-0003-01]; 'Fondation pour la Recherche Medicale' (FRM) [DBF20160635724]; ANR [ANR-19-CE45-0023-02, ANR-19-CE12-0006-01]; CNRS; Universite de Paris; 'Consejo Nacional de Ciencia y Tecnologia' (CONACyT) [ANRS-A02019-2 ECTZ108689]; Agence Nationale de la Recherche contre le SIDA fellowship [ANRS-A02019-2 ECTZ108689]; ANR-15-CE12-0003,sRNA-FIT,Adaptation par ARN régulateurs chez Staphylococcus aureus(2015); ANR-19-CE45-0023,PaRNAssus,Décrypter les architectures complexes d'ARN par sondage et interactions(2019); ANR-19-CE12-0006,RRARE,ARN Régulateurs et Résistance aux Antibiotiques(2019); Jonchère, Laurent; Adaptation par ARN régulateurs chez Staphylococcus aureus - - sRNA-FIT2015 - ANR-15-CE12-0003 - AAPG2015 - VALID; Décrypter les architectures complexes d'ARN par sondage et interactions - - PaRNAssus2019 - ANR-19-CE45-0023 - AAPG2019 - VALID; ARN Régulateurs et Résistance aux Antibiotiques - - RRARE2019 - ANR-19-CE12-0006 - AAPG2019 - VALID
نبذة مختصرة : Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.
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