Role of the ATP-dependent chromatin remodeling enzyme Fun30/Smarcad1 in the regulation of mRNA splicing

Biochem Biophys Res Commun. 2020 May 28;526(2):453-458. doi: 10.1016/j.bbrc.2020.02.175. Epub 2020 Mar 28.

Abstract

The yeast ATP-dependent chromatin remodeling enzyme Fun30 has been shown to regulate heterochromatin silencing, DNA repair, transcription, and chromatin organization. Although chromatin structure has been proposed to influence splice site recognition and regulation, whether ATP-dependent chromatin remodeling enzyme plays a role in regulating splicing is not known. In this study, we find that pre-mRNA splicing efficiency is impaired and the recruitment of spliceosome is compromised in Fun30-depleted cells. In addition, Fun30 is enriched in the gene body of individual intron-containing genes. Moreover, we show that pre-mRNA splicing efficiency is dependent on the chromatin remodeling activity of Fun30. The function of Fun30 in splicing is further supported by the observation that, Smarcad1, the mammalian homolog of Fun30, regulates alternative splicing. Taken together, these results provide evidence for a novel role of Fun30 in regulating splicing.

Keywords: Alternative splicing; Chromatin remodeling; Fun30; Pre-mRNA splicing; Smarcad1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Chromatin / metabolism*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • RNA Splicing / genetics*
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Chromatin
  • FUN30 protein, S cerevisiae
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Adenosine Triphosphate
  • DNA Helicases
  • Smarcad1 protein, mouse