Translational efficiency across healthy and tumor tissues is proliferation-related

Xavier Hernandez-Alias, Hannah Benisty, Martin H. Schaefer, Luis Serrano

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere9275
JournalMolecular Systems Biology
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 1 2020

Keywords

  • codon usage
  • The Cancer Genome Atlas
  • tissue
  • translation
  • tRNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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