Most eukaryotic genes are interrupted by non-coding sequences known as introns which must be removed by pre-mRNA splicing mechanisms so that the coding sequences of nascent transcripts can be joined into contiguous mature mRNA molecules for protein production by the ribosome. Pre-mRNA splicing is a major form of post-transcriptional regulation of eukaryotic gene expression, and the molecular machine which catalyses the splicing reactions, a large ribonucleoprotein complex known as the spliceosome, is extremely complex, consisting of five U-type small nuclear ribonucleoprotein particles (snRNPs) and additional splicing factors. Even though several atomic resolution structures of large macromolecular complexes, such as RNA polymerase II and the ribosome, have been solved, the structure of the spliceosome is technically more challenging, as the complex is dynamic both in terms of composition and spatial organization. For this reason, structural studies of mRNA splicing focus on snRNPs rather than the spliceosome as a whole. In a recent report in the EMBO Journal1, Professor Ruiming Xu reports work from a collaboration with the New York University School of Medicine on the SF3a complex of the U2 snRNP, an evolutionarily conserved heterotrimeric complex that is essential for pre-mRNA splicing. The mechanism underlying its function has been unclear. Peichun Lin and Professor Xu together identified a core domain of the yeast SF3a complex that is required for complex assembly and solved its crystal structure by multiwavelength anomalous dispersion (MAD) at a resolution of 3.1 Å. They demonstrate that this domain is a bifurcated assembly of three subunits, Prp9, Prp11 and Prp21, with Prp9 interacting with Prp21 via a bidentate-binding mode, and Prp21 wrapping around Prp11. Using structure-guided biochemical analyses they show that Prp9 harbours a major binding site for stem-loop IIa of U2 snRNA. This study, funded by the National Natural Science Foundation of China and a Novo Nordisk-CAS Great Wall Professorship, identifies the structural basis for the assembly of the SF3a complex and offers important mechanistic insights into its function in the maturation of U2 snRNP.

1. Lin P.C. and Xu R.M. (2012) Structure and assembly of the SF3a splicing factor complex of U2 snRNP. The EMBO Journal 31, 1579–1590.

Figure 2. Overall structure of the SF3a core. (A) A ribbon representation of the core domain of the Prp9–Prp21–Prp11 complex. Prp9 is shown in green, Prp21 in magenta and Prp11 in cyan. Dashed lines denote disordered segments in the structure. A Cys2His2 U1C-type zinc finger (zinc atom shown as a sphere) of Prp9 and the SURP2 domains of Prp21 are indicated. (B) An orthogonal view of the heterotrimeric complex is shown in a surface representation with electrostatic potential distribution (blue, positively charged; red, negatively charged; white, neutral). The encircled area indicates the Prp9 region surrounding the zinc finger.

© 2012 European Molecular Biology Organization.