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| Item Type: | Article |
|---|---|
| Title: | Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain |
| Creators Name: | Rogelj, B., Easton, L.E., Bogu, G.K., Stanton, L.W., Rot, G., Curk, T., Zupan, B., Sugimoto, Y., Modic, M., Haberman, N., Tollervey, J., Fujii, R., Takumi, T., Shaw, C.E. and Ule, J. |
| Abstract: | Fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43) are RNA-binding proteins pathogenetically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but it is not known if they regulate the same transcripts. We addressed this question using crosslinking and immunoprecipitation (iCLIP) in mouse brain, which showed that FUS binds along the whole length of the nascent RNA with limited sequence specificity to GGU and related motifs. A saw-tooth binding pattern in long genes demonstrated that FUS remains bound to pre-mRNAs until splicing is completed. Analysis of FUS(-/-) brain demonstrated a role for FUS in alternative splicing, with increased crosslinking of FUS in introns around the repressed exons. We did not observe a significant overlap in the RNA binding sites or the exons regulated by FUS and TDP-43. Nevertheless, we found that both proteins regulate genes that function in neuronal development. |
| Keywords: | Alternative Splicing, Base Sequence, Brain, DNA-Binding Proteins, Exons, Gene Expression Regulation, Gene Order, Knockout Mice, Neurons, Protein Binding, RNA Isoforms, RNA Precursors, RNA-Binding Protein FUS, Animals, Mice |
| Source: | Scientific Reports |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 2 |
| Page Range: | 603 |
| Date: | 28 August 2012 |
| Official Publication: | https://doi.org/10.1038/srep00603 |
| PubMed: | View item in PubMed |
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