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  Translational regulation shapes the molecular landscape of complex disease phenotypes

Schafer, S., Adami, E., Heinig, M., Rodrigues, K. E., Kreuchwig, F., Silhavy, J., et al. (2015). Translational regulation shapes the molecular landscape of complex disease phenotypes. Nat Commun, 6: 6:7200. doi:10.1038/ncomms8200.

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© 2015 Macmillan Publishers Limited

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Schafer, S., Author
Adami, E., Author
Heinig, M.1, Author           
Rodrigues, K. E., Author
Kreuchwig, F., Author
Silhavy, J., Author
van Heesch, S., Author
Simaite, D., Author
Rajewsky, N., Author
Cuppen, E., Author
Pravenec, M., Author
Vingron, M.2, Author           
Cook, S. A., Author
Hubner, N., Author
Affiliations:
1Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
2Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 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.

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Language(s): eng - English
 Dates: 2015-05-26
 Publication Status: Published online
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 Identifiers: DOI: 10.1038/ncomms8200
ISSN: 2041-1723 (Electronic)
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Title: Nat Commun
  Alternative Title : Nature communications
Source Genre: Journal
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Pages: - Volume / Issue: 6 Sequence Number: 6:7200 Start / End Page: - Identifier: -