The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes

Nat Struct Mol Biol. 2015 Feb;22(2):138-44. doi: 10.1038/nsmb.2951. Epub 2015 Jan 19.

Abstract

Aquarius is a multifunctional putative RNA helicase that binds precursor-mRNA introns at a defined position. Here we report the crystal structure of human Aquarius, revealing a central RNA helicase core and several unique accessory domains, including an ARM-repeat domain. We show that Aquarius is integrated into spliceosomes as part of a pentameric intron-binding complex (IBC) that, together with the ARM domain, cross-links to U2 snRNP proteins within activated spliceosomes; this suggests that the latter aid in positioning Aquarius on the intron. Aquarius's ARM domain is essential for IBC formation, thus indicating that it has a key protein-protein-scaffolding role. Finally, we provide evidence that Aquarius is required for efficient precursor-mRNA splicing in vitro. Our findings highlight the remarkable structural adaptations of a helicase to achieve position-specific recruitment to a ribonucleoprotein complex and reveal a new building block of the human spliceosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Imidodiphosphate / chemistry
  • Adenylyl Imidodiphosphate / metabolism
  • Crystallography, X-Ray
  • Humans
  • Introns / genetics
  • Protein Binding / genetics
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Helicases / chemistry*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Splicing / genetics
  • Ribonucleoprotein, U2 Small Nuclear / chemistry
  • Ribonucleoprotein, U2 Small Nuclear / metabolism
  • Spliceosomes / metabolism*

Substances

  • Ribonucleoprotein, U2 Small Nuclear
  • Adenylyl Imidodiphosphate
  • RNA Helicases

Associated data

  • PDB/4PJ3