title: The RNA helicase Aquarius exhibits structural adaptations mediating its recruitment to spliceosomes.
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.
authors.affiliation: Macromolecular Crystallography, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Inessa
authors.initials: I
authors.lastname: De
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Sergey
authors.initials: S
authors.lastname: Bessonov
authors.affiliation: Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Romina
authors.initials: R
authors.lastname: Hofele
authors.affiliation: Department of Structural Biochemistry, Free University, Berlin, Germany.
authors.forename: Karine
authors.initials: K
authors.lastname: dos Santos
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Will
authors.affiliation: 1] Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. [2] Bioanalytics, Department of Clinical Chemistry, University Medical Center, Göttingen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
authors.affiliation: Macromolecular Crystallography, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pena
mesh_terms: D000266:Adenylyl Imidodiphosphate / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D007438:Introns / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000737:chemistry / Q000378:metabolism; D017381:Spliceosomes / Q000378:metabolism*
chemical_list: D017413:Ribonucleoprotein, U2 Small Nuclear; D000266:Adenylyl Imidodiphosphate; D020365:RNA Helicases