CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome

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• dc.contributor.author Jungfleisch, Jennifer, 1986-
• dc.contributor.author Böttcher, René
• dc.contributor.author Talló Parra, Marc, 1992-
• dc.contributor.author Pérez Vilaró, Gemma, 1985-
• dc.contributor.author Merits, Andres
• dc.contributor.author Novoa, Eva Maria
• dc.contributor.author Díez Antón, Juana, 1962-
• dc.date.accessioned 2022-09-14T06:49:55Z
• dc.date.available 2022-09-14T06:49:55Z
• dc.date.issued 2022
• dc.description.abstract Ample evidence indicates that codon usage bias regulates gene expression. How viruses, such as the emerging mosquito-borne Chikungunya virus (CHIKV), express their genomes at high levels despite an enrichment in rare codons remains a puzzling question. Using ribosome footprinting, we analyze translational changes that occur upon CHIKV infection. We show that CHIKV infection induces codon-specific reprogramming of the host translation machinery to favor the translation of viral RNA genomes over host mRNAs with an otherwise optimal codon usage. This reprogramming was mostly apparent at the endoplasmic reticulum, where CHIKV RNAs show high ribosome occupancy. Mechanistically, it involves CHIKV-induced overexpression of KIAA1456, an enzyme that modifies the wobble U34 position in the anticodon of tRNAs, which is required for proper decoding of codons that are highly enriched in CHIKV RNAs. Our findings demonstrate an unprecedented interplay of viruses with the host tRNA epitranscriptome to adapt the host translation machinery to viral production.
• dc.description.sponsorship This work was supported by the Spanish Ministry of Science and Innovation (PID2019-106959RB-I00/AEI/10.13039/501100011033 and PCIN-2016-106 to JD and PGC2018-098152-A-100 to EMN) and by an institutional “María de Maeztu” Programme for Units of Excellence in R&D (CEX2018-000792-M) and by the 2017 SGR 909 grant from the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya. RB was a recipient of a Juan de la Cierva fellowship. Mass spectrometric analyses were performed in the CRG/UPF Proteomics Unit (Proteored, PRB3, grant PT17/0019 PE I + D + i 2013-2016, ISCIII and ERDF). We thank C. V. Nicchitta and S. Leidel for experimental advice and F. Gebauer and A. Meyerhans for fruitful discussions. We acknowledge the support of the MEIC to the EMBL partnership, Centro de Excelencia Severo Ochoa and CERCA Programme/Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Jungfleisch J, Böttcher R, Talló-Parra M, Pérez-Vilaró G, Merits A, Novoa EM, Díez J. CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome. Nat Commun. 2022 Aug 11;13(1):4725. DOI: 10.1038/s41467-022-31835-x
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-022-31835-x
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/54063
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2022 Aug 11;13(1):4725
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106959RB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-098152-A-100
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/PCIN-2016-106
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/GC2018-098152-A-100
• dc.rights © The Author(s) 2022. 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Methylation
• dc.subject.keyword tRNAs
• dc.subject.keyword Viral infection
• dc.subject.keyword Virus–host interactions
• dc.title CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion