ena-STUDY-MDC-09-10-2014-10:25:05:471-186
Ribosome profiling in mammalian tissue reveals extensive translational regulation in the cardiometabolic syndrome
The extent of translational control of gene expression in mammalian tissues remains largely unknown. We analyzed genome-wide RNA expression and ribosome occupancies in heart and liver tissues to investigate strain-specific translational regulation in disease-relevant tissues in the rat. For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. In addition we also find hundreds of strain-specific differences in gene expression at the level of translation only that are influencing protein levels beyond transcriptional regulation. By integrating genetic, transcriptional and translational datasets we identify distinct signatures in 3’UTR variation, RNA binding protein motifs, and miRNA expression associated with translational regulation. We document novel and extensive translational control of important metabolic and cardiac genes. Several genes associated with heart and liver traits in human genome wide association studies are regulated at the translational level. Capturing inter-individual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes.
The extent of translational control of gene expression in mammalian tissues remains largely unknown. We analyzed genome-wide RNA expression and ribosome occupancies in heart and liver tissues to investigate strain-specific translational regulation in disease-relevant tissues in the rat. For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. In addition we also find hundreds of strain-specific differences in gene expression at the level of translation only that are influencing protein levels beyond transcriptional regulation. By integrating genetic, transcriptional and translational datasets we identify distinct signatures in 3’UTR variation, RNA binding protein motifs, and miRNA expression associated with translational regulation. We document novel and extensive translational control of important metabolic and cardiac genes. Several genes associated with heart and liver traits in human genome wide association studies are regulated at the translational level. Capturing inter-individual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes.