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.

Inessa De ¹, Sergey Bessonov ², Romina Hofele ³, Karine dos Santos ⁴, Cindy L Will ², Henning Urlaub ⁵, Reinhard Lührmann ², Vladimir Pena ¹

Affiliations

1 Macromolecular Crystallography, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
2 Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
3 Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
4 Department of Structural Biochemistry, Free University, Berlin, Germany.
5 1] Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. [2] Bioanalytics, Department of Clinical Chemistry, University Medical Center, Göttingen, Germany.

PMID: 25599396 DOI: 10.1038/nsmb.2951

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.