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

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 transla...

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Autores principales: Jungfleisch, Jennifer, Böttcher, René, Talló-Parra, Marc, Pérez-Vilaró, Gemma, Merits, Andres, Novoa, Eva Maria, Díez, Juana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366759/
https://www.ncbi.nlm.nih.gov/pubmed/35953468
http://dx.doi.org/10.1038/s41467-022-31835-x
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author Jungfleisch, Jennifer
Böttcher, René
Talló-Parra, Marc
Pérez-Vilaró, Gemma
Merits, Andres
Novoa, Eva Maria
Díez, Juana
author_facet Jungfleisch, Jennifer
Böttcher, René
Talló-Parra, Marc
Pérez-Vilaró, Gemma
Merits, Andres
Novoa, Eva Maria
Díez, Juana
author_sort Jungfleisch, Jennifer
collection PubMed
description 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.
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spelling pubmed-93667592022-08-11 CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome Jungfleisch, Jennifer Böttcher, René Talló-Parra, Marc Pérez-Vilaró, Gemma Merits, Andres Novoa, Eva Maria Díez, Juana Nat Commun Article 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. Nature Publishing Group UK 2022-08-11 /pmc/articles/PMC9366759/ /pubmed/35953468 http://dx.doi.org/10.1038/s41467-022-31835-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Jungfleisch, Jennifer
Böttcher, René
Talló-Parra, Marc
Pérez-Vilaró, Gemma
Merits, Andres
Novoa, Eva Maria
Díez, Juana
CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
title CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
title_full CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
title_fullStr CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
title_full_unstemmed CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
title_short CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome
title_sort chikv infection reprograms codon optimality to favor viral rna translation by altering the trna epitranscriptome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9366759/
https://www.ncbi.nlm.nih.gov/pubmed/35953468
http://dx.doi.org/10.1038/s41467-022-31835-x
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