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

Piotr Wysoczański, Cornelius Schneider, ShengQi Xiang, Francesca Munari, Simon Trowitzsch, Markus C Wahl, Reinhard Lührmann, Stefan Becker, Markus Zweckstetter

Nature structural & molecular biology 2014 Oct

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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.

Citation

Piotr Wysoczański, Cornelius Schneider, ShengQi Xiang, Francesca Munari, Simon Trowitzsch, Markus C Wahl, Reinhard Lührmann, Stefan Becker, Markus Zweckstetter. Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex. Nature structural & molecular biology. 2014 Oct;21(10):911-8