Translational regulation shapes the molecular landscape of complex disease phenotypes.

Title: Translational regulation shapes the molecular landscape of complex disease phenotypes.
Author(s): Schafer, S
Adami, E
Heinig, M
Rodrigues, KEC
Kreuchwig, F
Silhavy, J
Van Heesch, S
Simaite, D
Rajewsky, N
Cuppen, E
Pravenec, M
Vingron, M
Cook, SA
Hubner, N
Item Type: Journal Article
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 Date: 26-May-2015
Date of Acceptance: 17-Apr-2015
URI: http://hdl.handle.net/10044/1/51901
DOI: https://dx.doi.org/10.1038/ncomms8200
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 6
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 241504
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Animals
Gene Expression Regulation
Hypertension
Liver
Male
Myocardium
Phenotype
Proteome
Rats, Inbred BN
Rats, Inbred SHR
Ribosomes
Sequence Analysis, RNA
Myocardium
Liver
Ribosomes
Animals
Rats, Inbred BN
Rats, Inbred SHR
Hypertension
Proteome
Sequence Analysis, RNA
Gene Expression Regulation
Phenotype
Male
Animals
Gene Expression Regulation
Hypertension
Liver
Male
Myocardium
Phenotype
Proteome
Rats, Inbred BN
Rats, Inbred SHR
Ribosomes
Sequence Analysis, RNA
MD Multidisciplinary
Publication Status: Published online
Article Number: 7200
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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