Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex

Nat Struct Mol Biol. 2014 Oct;21(10):911-8. doi: 10.1038/nsmb.2889. Epub 2014 Sep 14.

Abstract

The precursor mRNA (pre-mRNA) retention and splicing (RES) complex is a spliceosomal complex that is present in yeast and humans and is important for RNA splicing and retention of unspliced pre-mRNA. Here, we present the solution NMR structure of the RES core complex from Saccharomyces cerevisiae. Complex formation leads to an intricate folding of three components-Snu17p, Bud13p and Pml1p-that stabilizes the RNA-recognition motif (RRM) fold of Snu17p and increases binding affinity in tertiary interactions between the components by more than 100-fold compared to that in binary interactions. RES interacts with pre-mRNA within the spliceosome, and through the assembly of the RES core complex RNA binding efficiency is increased. The three-dimensional structure of the RES core complex highlights the importance of cooperative folding and binding in the functional organization of the spliceosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / ultrastructure*
  • Nucleic Acid Conformation
  • RNA Precursors / genetics*
  • RNA Splicing
  • RNA, Fungal / metabolism
  • RNA-Binding Proteins / ultrastructure
  • Ribonucleoprotein, U2 Small Nuclear / genetics
  • Ribonucleoprotein, U2 Small Nuclear / ultrastructure*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / ultrastructure*
  • Spliceosomes / genetics

Substances

  • BUD13 homolog protein, human
  • Bud13 protein, S cerevisiae
  • Carrier Proteins
  • IST3 protein, S cerevisiae
  • Pml1 protein, S cerevisiae
  • RNA Precursors
  • RNA, Fungal
  • RNA-Binding Proteins
  • Ribonucleoprotein, U2 Small Nuclear
  • Saccharomyces cerevisiae Proteins