hnRNP A1 Regulates Alternative Splicing of Tau Exon 10 by Targeting 3' Splice Sites

Cells. 2020 Apr 10;9(4):936. doi: 10.3390/cells9040936.

Abstract

The ratio control of 4R-Tau/3R-Tau by alternative splicing of Tau exon 10 is important for maintaining brain functions. In this study, we show that hnRNP A1 knockdown induces inclusion of endogenous Tau exon 10, conversely, overexpression of hnRNP A1 promotes exon 10 skipping of Tau. In addition, hnRNP A1 inhibits splicing of intron 9, but not intron 10. Furthermore, hnRNP A1 directly interacts with the 3' splice site of exon 10 to regulate its functions in alternative splicing. Finally, gene ontology analysis demonstrates that hnRNP A1-induced splicing and gene expression targets a subset of genes with neuronal function.

Keywords: Tau; alternative splicing; exon 10; hnRNP A1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Exons / genetics*
  • Heterogeneous Nuclear Ribonucleoprotein A1 / genetics*
  • Humans
  • RNA Splice Sites / genetics*
  • Transfection
  • tau Proteins / genetics*

Substances

  • Heterogeneous Nuclear Ribonucleoprotein A1
  • RNA Splice Sites
  • tau Proteins