Disease-associated mutation inSRSF2misregulates splicing by altering RNA-binding affinities

Serine/arginine-rich splicing factor 2 (SRSF2) is an RNA-binding protein that plays important roles in splicing of mRNA precursors.SRSF2mutations are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how these mutations affect SRSF2 function has only begun to be...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2015-08, Vol.112 (34), p.E4726-E4734
Main Authors: Zhang, Jian, Lieu, Yen K., Ali, Abdullah M., Penson, Alex, Reggio, Kathryn S., Rabadan, Raul, Raza, Azra, Mukherjee, Siddhartha, Manley, James L.
Format: Article
Language:English
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Summary:Serine/arginine-rich splicing factor 2 (SRSF2) is an RNA-binding protein that plays important roles in splicing of mRNA precursors.SRSF2mutations are frequently found in patients with myelodysplastic syndromes and certain leukemias, but how these mutations affect SRSF2 function has only begun to be examined. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease to introduce the P95H mutation toSRSF2in K562 leukemia cells, generating an isogenic model so that splicing alterations can be attributed solely to mutant SRSF2. We found that SRSF2 (P95H) misregulates 548 splicing events (
ISSN:0027-8424
1091-6490