Translational efficiency across healthy and tumor tissues is proliferation‐related

Abstract

Background Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon-anticodon co-adaptation in humans is not completely understood, as well as its effect on tissue-specific protein levels. Results We first validated the accuracy of small RNA-seq for tRNA quantification across five human cell lines. We then analyzed tRNA expression in more than 8000 tumor samples from TCGA, together with their paired mRNA-seq and proteomics data, to determine the Relative Translation Efficiency. We thereby elucidate that the dynamic adaptation of the tRNA pool is largely related to the proliferative state across tissues, which determines tissue-specific translation efficiency. Furthermore, the aberrant translational efficiency of ProCCA and GlyGGT in cancer, among other codons, which is partly regulated by the tRNA gene copy numbers and their promoter DNA methylation, is associated with poor patient survival. Conclusions The distribution of tissue-specific tRNA pools over the whole cellular translatome affects the subsequent translational efficiency, which functionally determines a condition-specific expression program in tissues both in healthy and tumor states. * TCGA : The Cancer Genome Atlas PCA : Principal Component Analysis GSEA : Gene Set Enrichment Analysis RAA : Relative Anticodon Abundance RTE : Relative Translation Efficiency RTEw : RTE weights tAI : tRNA Adaptation Index RtAI : Relative tAI CNA : Copy Number Alteration BLCA : Bladder Urothelial Carcinoma BRCA : Breast invasive carcinoma CESC : Cervical squamous cell carcinoma and endocervical adenocarcinoma CHOL : Cholangiocarcinoma COAD : Colon adenocarcinoma ESCA : Esophageal carcinoma GBM : Glioblastoma multiforme HNSC : Head and Neck squamous cell carcinoma KICH : Kidney Chromophobe KIRC : Kidney renal clear cell carcinoma KIRP : Kidney renal papillary cell carcinoma LIHC : Liver hepatocellular carcinoma LUAD : Lung adenocarcinoma LUSC : Lung squamous cell carcinoma PAAD : Pancreatic adenocarcinoma PCPG : Pheochromocytoma and Paraganglioma PRAD : Prostate adenocarcinoma READ : Rectum adenocarcinoma SKCM : Skin Cutaneous Melanoma STAD : Stomach adenocarcinoma THCA : Thyroid carcinoma THYM : Thymoma UCEC : Uterine Corpus Endometrial Carcinoma