The landscape of the non-canonical RNA-binding site of Gemin5 unveils a feedback loop counteracting the negative effect on translation

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• dc.contributor.author Francisco-Velilla, Rosario
• dc.contributor.author Fernández-Chamorro, Javier
• dc.contributor.author Dotu, Ivan
• dc.contributor.author Martinez Salas, Encarnación
• dc.date.accessioned 2019-06-21T07:41:18Z
• dc.date.available 2019-06-21T07:41:18Z
• dc.date.issued 2018
• dc.description.abstract Gemin5 is a predominantly cytoplasmic protein that downregulates translation, beyond controlling snRNPs assembly. The C-terminal region harbors a non-canonical RNA-binding site consisting of two domains, RBS1 and RBS2, which differ in RNA-binding capacity and the ability to modulate translation. Here, we show that these domains recognize distinct RNA targets in living cells. Interestingly, the most abundant and exclusive RNA target of the RBS1 domain was Gemin5 mRNA. Biochemical and functional characterization of this target demonstrated that RBS1 polypeptide physically interacts with a predicted thermodynamically stable stem-loop upregulating mRNA translation, thereby counteracting the negative effect of Gemin5 protein on global protein synthesis. In support of this result, destabilization of the stem-loop impairs the stimulatory effect on translation. Moreover, RBS1 stimulates translation of the endogenous Gemin5 mRNA. Hence, although the RBS1 domain downregulates global translation, it positively enhances translation of RNA targets carrying thermodynamically stable secondary structure motifs. This mechanism allows fine-tuning the availability of Gemin5 to play its multiple roles in gene expression control.
• dc.description.sponsorship MINECO [BFU2014-54564, BIO2015-72716-EXP]; Comunidad de Madrid [B2017/BMD-3770]; Institutional grant from Fundación Ramón Areces. Funding for open access charge: MINECO [BIO2015-72716-EXP].
• dc.format.mimetype application/pdf
• dc.identifier.citation Francisco-Velilla R, Fernandez-Chamorro J, Dotu I, Martinez-Salas E. The landscape of the non-canonical RNA-binding site of Gemin5 unveils a feedback loop counteracting the negative effect on translation. Nucleic Acids Res. 2018 Aug 21;46(14):7339-53. DOI: 10.1093/nar/gky361
• dc.identifier.doi http://dx.doi.org/10.1093/nar/gky361
• dc.identifier.issn 0305-1048
• dc.identifier.uri http://hdl.handle.net/10230/41855
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Nucleic Acids Research. 2018 Aug 21;46(14):7339-53
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54564
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2015-72716-EXP
• dc.rights Copyright © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact moc.puo@snoissimrep.slanruoj
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Gene expression
• dc.subject.other Protein interaction
• dc.title The landscape of the non-canonical RNA-binding site of Gemin5 unveils a feedback loop counteracting the negative effect on translation
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion