Serine Rich Splicing Factor 2 (SRSF2) Flips for RNA Binding

Abstract

Mistakes in alternative splicing of RNA cause diseases such as acute myeloid leukemia. Serine Rich Splicing Factor 2 (SRSF2) is a splicing factor that controls alternative splicing by promoting exon inclusion, so it is not surprising that mutations to SRFS2 are linked to cancers. SR proteins harbor an RNA recognition motif (RRM) at the N‐terminus that binds to mRNA. SRSF2 has the unusual ability to bind to both pyrimidine and purine rich RNA sequences by flipping two C or G nucleotides in the mRNA into anti or syn orientations. The RRM specifically recognizes only C2, C3, and G5. Arg61 forms a hydrogen bond to C3, Phe59 hydrogen bonds to C2, and Lys17 is involved in flipping C2 or G2 into syn or anti conformations. Tyr92 binds with C2 and forms a hydrogen bond with C3. The mutation Pro95His binds better to UCCAGU and has been linked to cancer. The Hartford Union High School SMART (Students Modeling A Research Topic) Team modeled SRSF2 using 3D printing technology to highlight structural characteristics involved in RNA binding. Additional research on SRSF2 mutations and sequence binding has the potential to find both causes of and treatments for diseases like cancer.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973) for their support in funding the 2017‐2018 SMART Team Team program.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.