Translational efficiency across healthy and tumor tissues is proliferation-related.

Molecular Systems Biology
Xavier Hernandez-AliasLuis Serrano

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.

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Citations

Nov 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Hannah BenistyLuis Serrano
Mar 12, 2021·Wiley Interdisciplinary Reviews. RNA·J J David HoPhilip A Marsden
Mar 18, 2021·Cell Reports·Xavier Hernandez-AliasLuis Serrano
May 13, 2021·Nature Communications·Sungsam GongD Stephen Charnock-Jones
Jan 15, 2021·Annual Review of Biochemistry·Yi LiuFangzhou Zhao
Nov 14, 2020·Cell·Shensi ShenCaroline Robert

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Methods Mentioned

BETA
PCA
PCR

Software Mentioned

BBMap
Codon Pair Usage Tables ( CoCoPUTs )
GATK UnifiedGenotyper
GSEA
Segemehl
Hydro
GATK IndelRealigner
BLAST
SE
tRNAscan

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