TY - JOUR
T1 - Translational efficiency across healthy and tumor tissues is proliferation-related
AU - Hernandez-Alias, Xavier
AU - Benisty, Hannah
AU - Schaefer, Martin H.
AU - Serrano, Luis
N1 - Funding Information:
We thank Eva Maria Novoa Pardo, Samuel Miravet-Verde, and Marc Weber for stimulating and critical discussions. We thank the CRG Genomics Unit for assistance with RNA sequencing services. The results published here are in part based on data generated by the TCGA Research Network: https://www.cancer.gov/tcga. 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 Fundaci?n Ram?n Areces.
Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY 4.0 license
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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.
AB - 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.
KW - codon usage
KW - The Cancer Genome Atlas
KW - tissue
KW - translation
KW - tRNA
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U2 - 10.15252/msb.20199275
DO - 10.15252/msb.20199275
M3 - Article
C2 - 32149479
AN - SCOPUS:85081528956
VL - 16
JO - Molecular Systems Biology
JF - Molecular Systems Biology
SN - 1744-4292
IS - 3
M1 - e9275
ER -