HP1γ binding pre-mRNA intronic repeats modulates RNA splicing decisions

EMBO Rep. 2021 Sep 6;22(9):e52320. doi: 10.15252/embr.202052320. Epub 2021 Jul 27.

Abstract

HP1 proteins are best known as markers of heterochromatin and gene silencing. Yet, they are also RNA-binding proteins and the HP1γ/CBX3 family member is present on transcribed genes together with RNA polymerase II, where it regulates co-transcriptional processes such as alternative splicing. To gain insight in the role of the RNA-binding activity of HP1γ in transcriptionally active chromatin, we have captured and analysed RNAs associated with this protein. We find that HP1γ is specifically targeted to hexameric RNA motifs and coincidentally transposable elements of the SINE family. As these elements are abundant in introns, while essentially absent from exons, the HP1γ RNA association tethers unspliced pre-mRNA to chromatin via the intronic regions and limits the usage of intronic cryptic splice sites. Thus, our data unveil novel determinants in the relationship between chromatin and co-transcriptional splicing.

Keywords: Cbx3; HP1; RNA; chromatin; splicing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Introns / genetics
  • RNA Precursors* / genetics
  • RNA Precursors* / metabolism
  • RNA Splicing* / genetics
  • RNA-Binding Proteins

Substances

  • RNA Precursors
  • RNA-Binding Proteins