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

Translational regulation shapes the molecular landscape of complex disease phenotypes.

Author information

1
1] Cardiovascular and Metabolic Sciences, Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rossle-Strasse 10, 13125 Berlin, Germany [2] National Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore 169609, Singapore.
2
Cardiovascular and Metabolic Sciences, Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rossle-Strasse 10, 13125 Berlin, Germany.
3
1] Cardiovascular and Metabolic Sciences, Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rossle-Strasse 10, 13125 Berlin, Germany [2] Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
4
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenska 1083, 142 20 Prague 4, Czech Republic.
5
1] Systems Biology of Gene Regulatory Elements, Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rossle-Strasse 10, 13125 Berlin, Germany [2] DZHK (German Centre for Cardiovascular Research), Partner Site, 13347 Berlin, Germany.
6
Hubrecht Institute-KNAW &University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
7
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
8
1] National Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore 169609, Singapore [2] National Heart and Lung Institute, Imperial College London, London SW3 6NP, UK [3] Duke-National University of Singapore, Singapore 169857, Singapore.
9
1] Cardiovascular and Metabolic Sciences, Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Robert-Rossle-Strasse 10, 13125 Berlin, Germany [2] DZHK (German Centre for Cardiovascular Research), Partner Site, 13347 Berlin, Germany [3] Charité-Universitätsmedizin, 10117 Berlin, Germany.

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.

PMID:
26007203
PMCID:
PMC4455061
DOI:
10.1038/ncomms8200
[Indexed for MEDLINE]
Free PMC Article

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