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.
Footnotes
ABBREVIATIONS
- 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