Binding of SRSF4 to a novel enhancer modulates splicing of exon 6 of Fas pre-mRNA

Biochem Biophys Res Commun. 2018 Nov 30;506(3):703-708. doi: 10.1016/j.bbrc.2018.10.123. Epub 2018 Oct 28.

Abstract

Alternative splicing of exon 6 in Fas pre-mRNA generates a membrane bound pro-apoptotic isoform or soluble anti-apoptotic isoform. SRSF4 is a member of Arginine-Serine rich (SR) protein family. Here we demonstrate that increased SRSF4 expression stimulates exon 6 inclusion, and that reduced SRSF4 expression promotes exon 6 exclusion. We also show that weaker but not stronger 5' splice-site strength of exon 6 abolishes the SRSF4 effects on exon 6 splicing. Furthermore, we identified a novel enhancer on exon 6, on which SRSF4 interacts functionally and physically. Our results illustrate a novel regulatory mechanism of Fas pre-mRNA splicing.

Keywords: Alternative splicing; Exon 6; Fas; Pre-mRNA splicing; SRSF4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Enhancer Elements, Genetic / genetics*
  • Exons / genetics*
  • Gene Expression Regulation
  • HCT116 Cells
  • Humans
  • Protein Binding / genetics
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Splice Sites / genetics
  • RNA Splicing / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Serine-Arginine Splicing Factors / metabolism*
  • fas Receptor / genetics*
  • fas Receptor / metabolism

Substances

  • FAS protein, human
  • RNA Precursors
  • RNA Splice Sites
  • RNA, Messenger
  • SRSF4 protein, human
  • fas Receptor
  • Serine-Arginine Splicing Factors