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Translational efficiency across healthy and tumor tissues is proliferation-related

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dc.contributor.author Hernandez-Alias, Xavier
dc.contributor.author Benisty, Hannah, 1986-
dc.contributor.author Schaefer, Martin H.
dc.contributor.author Serrano Pubull, Luis, 1982-
dc.date.accessioned 2020-05-11T10:32:00Z
dc.date.available 2020-05-11T10:32:00Z
dc.date.issued 2020
dc.identifier.citation Hernandez-Alias X, Benisty H, Schaefer MH, Serrano L. Translational efficiency across healthy and tumor tissues is proliferation-related. Mol Syst Biol. 2020 Mar; 16(3):e 9275. DOI: 10.15252/msb.20199275
dc.identifier.issn 1744-4292
dc.identifier.uri http://hdl.handle.net/10230/44484
dc.description.abstract Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon-anticodon co-adaptation in humans is not completely understood, nor is its effect on tissue-specific protein levels. Here, we first validated the accuracy of small RNA-seq for tRNA quantification across five human cell lines. We then analyzed the tRNA abundance of more than 8,000 tumor samples from TCGA, together with their paired mRNA-seq and proteomics data, to determine the Supply-to-Demand Adaptation. We thereby elucidate that the dynamic adaptation of the tRNA pool is largely related to the proliferative state across tissues. The distribution of such tRNA pools over the whole cellular translatome affects the subsequent translational efficiency, which functionally determines a condition-specific expression program both in healthy and tumor states. Furthermore, the aberrant translational efficiency of some codons in cancer, exemplified by ProCCA and GlyGGT, is associated with poor patient survival. The regulation of these tRNA profiles is partly explained by the tRNA gene copy numbers and their promoter DNA methylation.
dc.description.sponsorship We acknowledge the support of the Spanish Ministry of Science and Innovation (MICINN), “Centro de Excelencia Severo Ochoa”, the CERCA Programme/Generalitat de Catalunya, and the Spanish Ministry of Science and Innovation (MICINN) to the EMBL partnership. The work of X.H. has been supported by a PhD fellowship from the Fundación Ramón Areces
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley-VCH Verlag
dc.relation.ispartof Molecular Systems Biology. 2020 Mar;16(3):e9275
dc.rights © 2020 by Xavier Hernandez-Alias et al. Published under the terms of the CC BY 4.0 license
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Càncer
dc.subject.other Tumors
dc.subject.other Genètica
dc.subject.other RNA
dc.subject.other Ús de codons
dc.title Translational efficiency across healthy and tumor tissues is proliferation-related
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.15252/msb.20199275
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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