4.4 Article

Crystal structure of U2 snRNP SF3b components: Hsh49p in complex with Cus1p-binding domain

Journal

RNA
Volume 23, Issue 6, Pages 968-981

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.059378.116

Keywords

splicing; U2 snRNP; SF3b; RNA binding; RRM

Funding

  1. Medical Research Council [MC_U105184330]
  2. Wellcome Trust
  3. MRC career development fellowship
  4. Humanitas Research Foundation
  5. CNRS
  6. CERBM-IGBMC
  7. INSERM
  8. French State fund
  9. Ligue Contre le Cancer
  10. [ANR-10LABX-0030-INRT]
  11. [ANR-10-IDEX-0002-02]
  12. MRC [MC_U105184330] Funding Source: UKRI
  13. Medical Research Council [MC_U105184330] Funding Source: researchfish

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Spliceosomal proteins Hsh49p and Cus1p are components of SF3b, which together with SF3a, Msl1p/Lea1p, Sm proteins, and U2 snRNA, form U2 snRNP, which plays a crucial role in pre-mRNA splicing. Hsh49p, comprising two RRMs, forms a heterodimer with Cus1p. We determined the crystal structures of Saccharomyces cerevisiae full-length Hsh49p as well as its RRM1 in complex with a minimal binding region of Cus1p (residues 290-368). The structures show that the Cus1 fragment binds to the a-helical surface of Hsh49p RRM1, opposite the four-stranded beta-sheet, leaving the canonical RNA-binding surface available to bind RNA. Hsh49p binds the 5' end region of U2 snRNA via RRM1. Its affinity is increased in complex with Cus1(290-368)p, partly because an extended RNA-binding surface forms across the protein-protein interface. The Hsh49p RRM1-Cus1(290-368)p structure fits well into cryo-EM density of the B-act spliceosome, corroborating the biological relevance of our crystal structure.

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