AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors

Nat Commun. 2016 Nov 8:7:13347. doi: 10.1038/ncomms13347.

Abstract

Alternative splicing of pre-mRNAs significantly contributes to the complexity of gene expression in higher organisms, but the regulation of the splice site selection remains incompletely understood. We have previously demonstrated that a chromatin-associated protein, AKAP95, has a remarkable activity in enhancing chromatin transcription. In this study, we show that AKAP95 interacts with many factors involved in transcription and RNA processing, including selective groups of hnRNP proteins, through its N-terminal region, and directly regulates pre-mRNA splicing. AKAP95 binds preferentially to proximal intronic regions on pre-mRNAs in human transcriptome, and this binding requires its zinc-finger domains. By selectively coordinating with hnRNP H/F and U proteins, AKAP95 appears to mainly promote the inclusion of many exons in the genome. AKAP95 also directly interacts with itself. Taken together, our results establish AKAP95 as a mostly positive regulator of pre-mRNA splicing and a possible integrator of transcription and splicing regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism*
  • Alternative Splicing / genetics*
  • Base Sequence
  • Exons / genetics
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Introns / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Binding
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA, Neoplasm / metabolism*
  • Transcription, Genetic

Substances

  • A Kinase Anchor Proteins
  • AKAP8 protein, human
  • FAM126A protein, human
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA Precursors
  • RNA, Neoplasm