TREX Exposes the RNA-binding Domain of Nxf1 to Enable mRNA Export

Nat Commun. 2012;3:1006. doi: 10.1038/ncomms2005.

Abstract

The metazoan TREX complex is recruited to mRNA during nuclear RNA processing and functions in exporting mRNA to the cytoplasm. Nxf1 is an mRNA export receptor, which binds processed mRNA and transports it through the nuclear pore complex. At present, the relationship between TREX and Nxf1 is not understood. Here we show that Nxf1 uses an intramolecular interaction to inhibit its own RNA-binding activity. When the TREX subunits Aly and Thoc5 make contact with Nxf1, Nxf1 is driven into an open conformation, exposing its RNA-binding domain, allowing RNA binding. Moreover, the combined knockdown of Aly and Thoc5 markedly reduces the amount of Nxf1 bound to mRNA in vivo and also causes a severe mRNA export block. Together, our data indicate that TREX provides a license for mRNA export by driving Nxf1 into a conformation capable of binding mRNA.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus
  • Exodeoxyribonucleases / chemistry
  • Exodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / metabolism*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleocytoplasmic Transport Proteins / chemistry
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Phosphoproteins / chemistry
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Transport*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ALYREF protein, human
  • NXF1 protein, human
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • Phosphoproteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • THOC5 protein, human
  • Transcription Factors
  • Exodeoxyribonucleases
  • three prime repair exonuclease 1