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学術論文

Translational regulation shapes the molecular landscape of complex disease phenotypes

MPS-Authors
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Heinig,  M.
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron,  M.
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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http://www.ncbi.nlm.nih.gov/pubmed/26007203
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Schafer.pdf
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引用

Schafer, S., Adami, E., Heinig, M., 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. (2015). Translational regulation shapes the molecular landscape of complex disease phenotypes. Nat Commun, 6:. doi:10.1038/ncomms8200.


引用: https://hdl.handle.net/11858/00-001M-0000-002A-3943-D
要旨
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.