Details

Autor(en) / Beteiligte

• Hernandez‐Alias, Xavier
• Benisty, Hannah
• Schaefer, Martin H
• Serrano, Luis

Titel

Translational efficiency across healthy and tumor tissues is proliferation‐related

Ist Teil von

• Molecular systems biology, 2020-03, Vol.16 (3), p.e9275-n/a

Ort / Verlag

England: EMBO Press

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Synopsis Quantification of tRNA expression over thousands of small RNA‐seq samples from The Cancer Genome Atlas unveils the existence of tissue‐specific translational efficiencies related to proliferation. tRNA abundance is tissue‐ and cancer‐type‐specific. Translational efficiency is globally controlled and the cellular translatome needs to compete for a limiting tRNA pool. Proliferation is the major determinant of translational efficiency differences among tissues, and the codon ProCCA appears particularly favored in cancer. Differences at the tRNA pool affect protein translation and subsequently determine specific functional phenotypes. Quantification of tRNA expression over thousands of small RNA‐seq samples from The Cancer Genome Atlas unveils the existence of tissue‐specific translational efficiencies related to proliferation.