期刊
MOLECULAR CELL
卷 73, 期 3, 页码 490-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2018.11.012
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资金
- National Centre for Competence in Research (NCCR) RNA & Disease - Swiss National Science Foundation
- NOMIS Foundation
- Sinergia grant [CRSII3_136222]
- Swiss National Science Foundation
- MRC [UKDRI-6005] Funding Source: UKRI
Fused in sarcoma (FUS) is an RNA binding protein involved in regulating many aspects of RNA processing and linked to several neurodegenerative diseases. Transcriptomics studies indicate that FUS binds a large variety of RNA motifs, suggesting that FUS RNA binding might be quite complex. Here, wepresent solution structures ofFUSzincfinger (ZnF) and RNA recognition motif (RRM) domains bound to RNA. These structures show a bipartite binding mode of FUS comprising of sequence-specific recognition of a NGGU motif via the ZnF and an unusual shape recognition of a stem-loop RNA via the RRM. In addition, sequence-independent interactions via the RGG repeats significantly increase binding affinity and promote destabilization of structured RNA conformation, enabling additional binding. We further show that disruption of the RRM and ZnF domains abolishes FUS function in splicing. Altogether, our results rationalize why deciphering the RNA binding mode of FUS has been so challenging.
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