Mutation bias within oncogene families is related to proliferation-specific codon usage

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• dc.contributor.author Benisty, Hannah, 1986-
• dc.contributor.author Weber, Marc
• dc.contributor.author Hernandez-Alias, Xavier
• dc.contributor.author Schaefer, Martin H.
• dc.contributor.author Serrano Pubull, Luis, 1982-
• dc.date.accessioned 2020-12-22T11:38:44Z
• dc.date.available 2020-12-22T11:38:44Z
• dc.date.issued 2020
• dc.description.abstract It is well known that in cancer gene families some members are more frequently mutated in tumor samples than their family counterparts. A paradigmatic case of this phenomenon is KRAS from the RAS family. Different explanations have been proposed ranging from differential interaction with other proteins to preferential expression or localization. Interestingly, it has been described that despite the high amino acid identity between RAS family members, KRAS employs an intriguing differential codon usage. Here, we found that this phenomenon is not exclusive to the RAS family. Indeed, in the RAS family and other oncogene families with two or three members, the most prevalently mutated gene in tumor samples employs a differential codon usage that is characteristic of genes involved in proliferation. Prompted by these observations, we chose the RAS family to experimentally demonstrate that the translation efficiency of oncogenes that are preferentially mutated in tumor samples is increased in proliferative cells compared to quiescent cells. These results were further validated by assessing the translation efficiency of KRAS in cell lines that differ in their tRNA expression profile. These differences are related to the cell division rate of the studied cells and thus suggest an important role in context-specific oncogene expression regulation. Altogether, our study demonstrates that dynamic translation programs contribute to shaping the expression profiles of oncogenes. Therefore, we propose this codon bias as a regulatory layer to control cell context-specific expression and explain the differential prevalence of mutations in certain members of oncogene families.
• dc.description.sponsorship The work of X.H.-A. has been supported by a PhD fellowship from the Fundación Ramón Areces. We acknowledge the support of the Spanish Ministry of Science and Innovation to the European Molecular Biology Laboratory partnership, the Centro de Excelencia Severo Ochoa and the Centres de Recerca de Catalunya Programme/Generalitat de Catalunya
• dc.format.mimetype application/pdf
• dc.identifier.citation Benisty H, Weber M , Hernandez-Alias X , Schaefer MH, Serrano L. Mutation bias within oncogene families is related to proliferation-specific codon usage. Proc Natl Acad Sci USA. 2020 Dec 1; 117(48): 30848-30856. DOI: 10.1073/pnas.2016119117
• dc.identifier.doi http://dx.doi.org/10.1073/pnas.2016119117
• dc.identifier.issn 0027-8424
• dc.identifier.uri http://hdl.handle.net/10230/46112
• dc.language.iso eng
• dc.publisher National Academy of Sciences
• dc.relation.ispartof Proceedings of the National Academy of Sciences of the United States of America. 2020 Dec 1;117(48):30848-56
• dc.rights © National Academy of Sciences
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Càncer
• dc.subject.other Tumors
• dc.subject.other Proteïnes
• dc.subject.other Oncogens
• dc.title Mutation bias within oncogene families is related to proliferation-specific codon usage
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion