Viral codon usage and the host transfer RNA

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• dc.contributor.author Muscolino, Elena
• dc.contributor.author Díez Antón, Juana, 1962-
• dc.date.accessioned 2025-11-07T14:32:10Z
• dc.date.available 2025-11-07T14:32:10Z
• dc.date.issued 2025
• dc.date.updated 2025-11-07T14:32:10Z
• dc.description.abstract The expansion of viruses within cells requires efficient viral protein production. Counterintuitively, many viral genomes are enriched in suboptimal codons, which are typically associated with reduced protein outputs. Recent research using chikungunya virus (CHIKV) as a prototype model highlights the role of host transfer RNA (tRNA) modifications, collectively known as the tRNA epitranscriptome, in resolving this paradox. Upon infection, CHIKV triggers a DNA damage stress response that ultimately leads to changes in the tRNA epitranscriptome. These changes reprogram codon optimality, selectively enhancing the translation of specific suboptimal codons that are highly enriched in both host stress response genes and the viral genome. Hence, CHIKV codon usage optimally aligns with the tRNA modification landscape in infected cells. We propose that this interplay between viral codon usage, stress responses, and tRNA modifications is a shared strategy among viruses beyond CHIKV. Targeting this interplay may pave the way for the development of broad-spectrum antiviral therapies.
• dc.description.sponsorship This work was supported by the Spanish Ministry of Science, Innovation and Universities (PID2022-136939OB-I00 funded by MICIU/AEI/10.13039/501100011033), by the 2021 SGR 00176 grant from the Departament de Recerca i Universitats de la Generalitat de Catalunya, and an institutional "María de Maeztu" Program for Units of Excellence in R&D (CEX2018-000792-M). E.M. was the recipient of Marie Sklodowska-Curie Grant Agreement 101065094. We thank Andreas Meyerhans for fruitful discussions.
• dc.format.mimetype application/pdf
• dc.identifier.citation Muscolino E, Diez J. Viral codon usage and the host transfer RNA. Annu Rev Virol. 2025 Sep;12(1):223-37. DOI: 10.1146/annurev-virology-092623-105418
• dc.identifier.doi http://dx.doi.org/10.1146/annurev-virology-092623-105418
• dc.identifier.issn 2327-056X
• dc.identifier.uri http://hdl.handle.net/10230/71810
• dc.language.iso eng
• dc.publisher Annual Reviews Inc
• dc.relation.ispartof Annual Review of Virology. 2025;12(1):223-37
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2022-136939OB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101065094
• dc.rights Copyright © 2025 by the author(s). This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword DNA damage response
• dc.subject.keyword Codon optimality
• dc.subject.keyword Codon usage
• dc.subject.keyword mcm5/mcm5s2
• dc.subject.keyword tRNA epitranscriptome
• dc.subject.keyword Viruses
• dc.title Viral codon usage and the host transfer RNA
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion