The m 6 A-methylase complex recruits TREX and regulates mRNA export

Sci Rep. 2018 Sep 14;8(1):13827. doi: 10.1038/s41598-018-32310-8.

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Recruitment of the TREX mRNA export complex to mRNA is driven by transcription, 5' capping and pre-mRNA splicing. Here we identify a fourth mechanism in human cells driving the association of TREX with mRNA involving the m6A methylase complex. We show that the m6A complex recruits TREX to m6A modified mRNAs and this process is essential for their efficient export. TREX also stimulates recruitment of the m6A reader protein YTHDC1 to the mRNA and the m6A complex influences the interaction of TREX with YTHDC1. Together our studies reveal a key role for TREX in the export of m6A modified mRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Adenosine / physiology
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Exodeoxyribonucleases / metabolism*
  • Exodeoxyribonucleases / physiology
  • HEK293 Cells
  • Humans
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Phosphoproteins / metabolism*
  • Phosphoproteins / physiology
  • RNA Splicing / physiology
  • RNA Splicing Factors / metabolism
  • RNA Transport / physiology*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism

Substances

  • NXF1 protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Phosphoproteins
  • RNA Splicing Factors
  • RNA, Messenger
  • RNA-Binding Proteins
  • YTHDC1 protein, human
  • N6-methyladenosine (m6A)
  • Exodeoxyribonucleases
  • three prime repair exonuclease 1
  • Adenosine