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Translational regulation shapes the molecular landscape of complex disease phenotypes

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Item Type:Article
Title:Translational regulation shapes the molecular landscape of complex disease phenotypes
Creators Name:Schafer, S. and Adami, E. and Heinig, M. and Costa Rodrigues, K.E. and Kreuchwig, F. and Silhavy, J. and van Heesch, S. and Simaite, D. and Rajewsky, N. and Cuppen, E. and Pravenec, M. and Vingron, M. and Cook, S.A. and Hubner, N.
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.
Keywords:Gene Expression Regulation, Hypertension, Liver, Myocardium, Phenotype, Proteome, Inbred BN Rats, Inbred SHR Rats, Ribosomes, RNA Sequence Analysis, Animals, Rats
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:6
Page Range:7200
Date:26 May 2015
Official Publication:https://doi.org/10.1038/ncomms8200
PubMed:View item in PubMed

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