HNRNPA2B1 Is a Mediator of m(6)A-Dependent Nuclear RNA Processing Events

Cell. 2015 Sep 10;162(6):1299-308. doi: 10.1016/j.cell.2015.08.011. Epub 2015 Aug 27.

Abstract

N(6)-methyladenosine (m(6)A) is the most abundant internal modification of messenger RNA. While the presence of m(6)A on transcripts can impact nuclear RNA fates, a reader of this mark that mediates processing of nuclear transcripts has not been identified. We find that the RNA-binding protein HNRNPA2B1 binds m(6)A-bearing RNAs in vivo and in vitro and its biochemical footprint matches the m(6)A consensus motif. HNRNPA2B1 directly binds a set of nuclear transcripts and elicits similar alternative splicing effects as the m(6)A writer METTL3. Moreover, HNRNPA2B1 binds to m(6)A marks in a subset of primary miRNA transcripts, interacts with the microRNA Microprocessor complex protein DGCR8, and promotes primary miRNA processing. Also, HNRNPA2B1 loss and METTL3 depletion cause similar processing defects for these pri-miRNA precursors. We propose HNRNPA2B1 to be a nuclear reader of the m(6)A mark and to mediate, in part, this mark's effects on primary microRNA processing and alternative splicing. PAPERCLIP.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Alternative Splicing
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Humans
  • Methylation
  • RNA / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA-Binding Proteins / metabolism
  • Transcriptome

Substances

  • DGCR8 protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • RNA-Binding Proteins
  • hnRNP A2
  • N(6)-methyladenosine
  • RNA
  • Adenosine

Associated data

  • GEO/GSE70061