A high-resolution structure of the pre-microRNA nuclear export machinery

Science. 2009 Nov 27;326(5957):1275-9. doi: 10.1126/science.1178705.

Abstract

Nuclear export of microRNAs (miRNAs) by exportin-5 (Exp-5) is an essential step in miRNA biogenesis. Here, we present the 2.9 angstrom structure of the pre-miRNA nuclear export machinery formed by pre-miRNA complexed with Exp-5 and a guanine triphosphate (GTP)-bound form of the small nuclear guanine triphosphatase (GTPase) Ran (RanGTP). The x-ray structure shows that Exp-5:RanGTP recognizes the 2-nucleotide 3' overhang structure and the double-stranded stem of the pre-miRNA. Exp-5:RanGTP shields the pre-miRNA stem from degradation in a baseball mitt-like structure where it is held by broadly distributed weak interactions, whereas a tunnel-like structure of Exp-5 interacts strongly with the 2-nucleotide 3' overhang through hydrogen bonds and ionic interactions. RNA recognition by Exp-5:RanGTP does not depend on RNA sequence, implying that Exp-5:RanGTP can recognize a variety of pre-miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Binding Sites
  • Chemical Phenomena
  • Crystallization
  • Crystallography, X-Ray
  • Dogs
  • Humans
  • Hydrogen Bonding
  • Karyopherins / chemistry*
  • Karyopherins / metabolism
  • MicroRNAs / chemistry*
  • MicroRNAs / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • ran GTP-Binding Protein / chemistry
  • ran GTP-Binding Protein / metabolism

Substances

  • Karyopherins
  • MicroRNAs
  • XPO5 protein, human
  • ran GTP-Binding Protein

Associated data

  • PDB/3A6P