Open AccessTranslational efficiency across healthy and tumor tissues is proliferation‐related
Author(s) -
HernandezAlias Xavier,
Benisty Hannah,
Schaefer Martin H,
Serrano Luis
Publication year - 2020
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20199275
Subject(s) - biology , computational biology , posttranslational modification , microbiology and biotechnology , cancer research , biochemistry , enzyme
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 ArgAGA, 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.