Impact of uORFs in mediating regulation of translation in stress conditions

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Moro, Simone G.
  • dc.contributor.author Hermans, Cedric
  • dc.contributor.author Ruiz Orera, Jorge, 1988-
  • dc.contributor.author Albà Soler, Mar
  • dc.date.accessioned 2021-09-02T06:24:42Z
  • dc.date.available 2021-09-02T06:24:42Z
  • dc.date.issued 2021
  • dc.description.abstract Background: A large fraction of genes contains upstream ORFs (uORFs) in the 5' untranslated region (5'UTR). The translation of uORFs can inhibit the translation of the main coding sequence, for example by causing premature dissociation of the two ribosomal units or ribosome stalling. However, it is currently unknown if most uORFs are inhibitory or if this activity is restricted to specific cases. Here we interrogate ribosome profiling data from three different stress experiments in yeast to gain novel insights into this question. Results: By comparing ribosome occupancies in different conditions and experiments we obtain strong evidence that, in comparison to primary coding sequences (CDS), which undergo translational arrest during stress, the translation of uORFs is mostly unaffected by changes in the environment. As a result, the relative abundance of uORF-encoded peptides increases during stress. In general, the changes in the translational efficiency of regions containing uORFs do not seem to affect downstream translation. The exception are uORFs found in a subset of genes that are significantly up-regulated at the level of translation during stress; these uORFs tend to be translated at lower levels in stress conditions than in optimal growth conditions, facilitating the translation of the CDS during stress. We find new examples of uORF-mediated regulation of translation, including the Gcn4 functional homologue fil1 and ubi4 genes in S. pombe. Conclusion: We find evidence that the relative amount of uORF-encoded peptides increases during stress. The increased translation of uORFs is however uncoupled from the general CDS translational repression observed during stress. In a subset of genes that encode proteins that need to be rapidly synthesized upon stress uORFs act as translational switches.
  • dc.description.sponsorship 1. Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) grants BFU2015–65235-P and PGC2018–094091-B-I00, co-funded by Fondo Europeo de Desarrollo Regional (FEDER); 2. Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya, grant 2017SGR01020; 3. Spanish National Bioinformatics Institute (INB), funded by ISCIII and FEDER, grant PT17/0009/0014 of the PE I + D + i 2013–2016.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Moro SG, Hermans C, Ruiz-Orera J, Albà MM. Impact of uORFs in mediating regulation of translation in stress conditions. BMC Mol Cell Biol. 2021;22(1):29. DOI: 10.1186/s12860-021-00363-9
  • dc.identifier.doi http://dx.doi.org/10.1186/s12860-021-00363-9
  • dc.identifier.issn 2661-8850
  • dc.identifier.uri http://hdl.handle.net/10230/48363
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof BMC Mol Cell Biol. 2021;22(1):29
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015–65235-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018–094091-B-I00
  • dc.rights © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.title Impact of uORFs in mediating regulation of translation in stress conditions
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Hospital del Mar Research Institute)
Articles (Departament de Medicina i Ciències de la Vida)