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dc.contributor.authorVinogradova, Daria S.
dc.contributor.authorZegarra, Victor
dc.contributor.authorMaksimova, Elena
dc.contributor.authorNakamoto, Jose Alberto
dc.contributor.authorKasatsky, Pavel
dc.contributor.authorPaleskava, Alena
dc.contributor.authorKonevega, Andrey L.
dc.contributor.authorMilón, Pohl
dc.date.accessioned2020-07-20T02:05:54Z
dc.date.available2020-07-20T02:05:54Z
dc.date.issued2020-01-01
dc.identifier.issn15449173
dc.identifier.doi10.1371/journal.pbio.3000593
dc.identifier.urihttp://hdl.handle.net/10757/652189
dc.description.abstractDuring host colonization, bacteria use the alarmones (p)ppGpp to reshape their proteome by acting pleiotropically on DNA, RNA, and protein synthesis. Here, we elucidate how the initiating ribosome senses the cellular pool of guanosine nucleotides and regulates the progression towards protein synthesis. Our results show that the affinity of guanosine triphosphate (GTP) and the inhibitory concentration of ppGpp for the 30S-bound initiation factor IF2 vary depending on the programmed mRNA. The TufA mRNA enhanced GTP affinity for 30S complexes, resulting in improved ppGpp tolerance and allowing efficient protein synthesis. Conversely, the InfA mRNA allowed ppGpp to compete with GTP for IF2, thus stalling 30S complexes. Structural modeling and biochemical analysis of the TufA mRNA unveiled a structured enhancer of translation initiation (SETI) composed of two consecutive hairpins proximal to the translation initiation region (TIR) that largely account for ppGpp tolerance under physiological concentrations of guanosine nucleotides. Furthermore, our results show that the mechanism enhancing ppGpp tolerance is not restricted to the TufA mRNA, as similar ppGpp tolerance was found for the SETI-containing Rnr mRNA. Finally, we show that IF2 can use pppGpp to promote the formation of 30S initiation complexes (ICs), albeit requiring higher factor concentration and resulting in slower transitions to translation elongation. Altogether, our data unveil a novel regulatory mechanism at the onset of protein synthesis that tolerates physiological concentrations of ppGpp and that bacteria can exploit to modulate their proteome as a function of the nutritional shift happening during stringent response and infection.en_US
dc.description.sponsorshipRussian Foundation for Basic Researchen_US
dc.formatapplication/pdfen_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.urlhttps://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000593en_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.sourceUniversidad Peruana de Ciencias Aplicadas (UPC)es_PE
dc.sourceRepositorio Academico - UPCes_PE
dc.titleHow the initiating ribosome copes with ppGpp to translate mRNAsen_US
dc.typeinfo:eu-repo/semantics/articleen_US
dc.identifier.eissn15457885
dc.identifier.journalPLoS Biologyen_US
dc.description.peerreviewRevisión por pareses_PE
dc.identifier.eid2-s2.0-85078947441
dc.identifier.scopusidSCOPUS_ID:85078947441
dc.source.journaltitlePLoS Biology
dc.source.volume18
dc.source.issue1
refterms.dateFOA2020-07-20T02:05:58Z
dc.identifier.isni0000 0001 2196 144X


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