Translational regulation shapes the molecular landscape of complex disease phenotypes

Schafer, S.; Adami, E.; Heinig, M.; Costa Rodrigues, K.E.; Kreuchwig, F.; Silhavy, J.; van Heesch, S.; Simaite, D.; Rajewsky, N.; Cuppen, E.; Pravenec, M.; Vingron, M.; Cook, S.A.; Hubner, N.

Translational regulation shapes the molecular landscape of complex disease phenotypes

Tools

	PDF (Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 877kB
	Other (Supplementary Data) 1MB

Item Type:	Article
Title:	Translational regulation shapes the molecular landscape of complex disease phenotypes
Creators Name:	Schafer, S., Adami, E., Heinig, M., Costa Rodrigues, K.E., Kreuchwig, F., Silhavy, J., van Heesch, S., Simaite, D., Rajewsky, N., Cuppen, E., Pravenec, M., Vingron, M., 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
Volume:	6
Page Range:	7200
Date:	26 May 2015
Official Publication:	https://doi.org/10.1038/ncomms8200
PubMed:	View item in PubMed

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year