Dissection of FUS domains involved in regulation of SnRNP70 gene expression

FEBS Lett. 2020 Nov;594(21):3518-3529. doi: 10.1002/1873-3468.13924. Epub 2020 Sep 20.

Abstract

FUS is one of the causative factors of amyotrophic lateral sclerosis. Loss and/or gain of its physiological functions has been believed to be linked to the pathogenesis of this condition. However, its functions remain incompletely understood. This study dissected the domains of FUS regulating the expression of SnRNP70, which functions in mRNA splicing. Biochemical analysis revealed that all FUS domains except for RGG1 contribute to determining Snrnp70 transcript abundance and thus its protein abundance. RNA-Seq analysis using the Gly-rich domain-deleted mutant coupled with snRNP70 knockdown revealed that FUS has a potential to regulate gene expression in both snRNP70-dependent and snRNP70-independent manners through the Gly-rich domain. These results provide insight into molecular details of the regulation of gene expression by FUS.

Keywords: FUS; RNA-Seq; conserved intron; gene expression; snRNP70.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Glycine / genetics
  • Glycine / metabolism
  • Humans
  • Introns / genetics
  • Mice
  • Neurons / metabolism
  • Protein Domains*
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Protein FUS / chemistry*
  • RNA-Binding Protein FUS / genetics
  • RNA-Binding Protein FUS / metabolism*
  • Ribonucleoprotein, U1 Small Nuclear / biosynthesis
  • Ribonucleoprotein, U1 Small Nuclear / genetics*
  • Ribonucleoprotein, U1 Small Nuclear / metabolism

Substances

  • RNA, Messenger
  • RNA-Binding Protein FUS
  • Ribonucleoprotein, U1 Small Nuclear
  • SNRNP70 protein, human
  • Snrnp70 protein, mouse
  • Glycine