Translational regulation shapes the molecular landscape of complex disease phenotypes

Nat Commun. 2015 May 26;6:7200. doi: 10.1038/ncomms8200.

Abstract

The extent of translational control of gene expression in mammalian tissues remains largely unknown. Here we perform genome-wide RNA sequencing and ribosome profiling in heart and liver tissues to investigate strain-specific translational regulation in the spontaneously hypertensive rat (SHR/Ola). For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. Remarkably, we observe hundreds of strain-specific differences in translation, almost doubling the number of differentially expressed genes. The integration of genetic, transcriptional and translational data sets reveals distinct signatures in 3'UTR variation, RNA-binding protein motifs and miRNA expression associated with translational regulation of gene expression. We show that a large number of genes associated with heart and liver traits in human genome-wide association studies are primarily translationally regulated. Capturing interindividual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Hypertension / metabolism*
  • Liver / metabolism*
  • Male
  • Myocardium / metabolism*
  • Phenotype
  • Proteome
  • Rats, Inbred BN
  • Rats, Inbred SHR
  • Ribosomes / metabolism*
  • Sequence Analysis, RNA

Substances

  • Proteome