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| 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 |
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