2026-04-17T15:56:06Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/540632025-12-12T04:18:14Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Jungfleisch, Jennifer, 1986- author Böttcher, René author Talló Parra, Marc, 1992- author Pérez Vilaró, Gemma, 1985- author Merits, Andres author Novoa, Eva Maria author Díez Antón, Juana, 1962- author 2022-09-14T06:49:55Z 2022-09-14T06:49:55Z 2022 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. 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. Methylation tRNAs Viral infection Virus–host interactions CHIKV infection reprograms codon optimality to favor viral RNA translation by altering the tRNA epitranscriptome