Structure of a yeast spliceosome at 3.6-angstrom resolution

Structure and function of the spliceosome When RNA is transcribed from DNA in the eukaryotic cell nucleus, the initial transcript includes noncoding introns that must be spliced out. This splicing is done by a complex macromolecular machine, the spliceosome, which comprises five small nuclear RNAs and more than 100 associated proteins. Now, two papers reveal insights into the structure and function of the yeast spliceosome. Yan et al. describe a high-resolution structure determined by electron microscopy of a spliceosome complex comprising four RNAs and 37 proteins. Hang et al. focus on the catalytic site and show how protein components anchor the transcribed RNA and allow sufficient flexibility to deliver RNA components involved in catalyzing the splicing reaction. Science, this issue pp. 1182 and 1191 A high-resolution structure determined by electron microscopy provides insight into how the spliceosome functions. Splicing of precursor messenger RNA (pre-mRNA) in yeast is executed by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs), NTC (nineteen complex), NTC-related proteins (NTR), and a number of associated enzymes and cofactors. Here, we report the three-dimensional structure of a Schizosaccharomyces pombe spliceosome at 3.6-angstrom resolution, revealed by means of single-particle cryogenic electron microscopy. This spliceosome contains U2 and U5 snRNPs, NTC, NTR, U6 small nuclear RNA, and an RNA intron lariat. The atomic model includes 10,574 amino acids from 37 proteins and four RNA molecules, with a combined molecular mass of approximately 1.3 megadaltons. Spp42 (Prp8 in Saccharomyces cerevisiae), the key protein component of the U5 snRNP, forms a central scaffold and anchors the catalytic center. Both the morphology and the placement of protein components appear to have evolved to facilitate the dynamic process of pre-mRNA splicing. Our near-atomic-resolution structure of a central spliceosome provides a molecular framework for mechanistic understanding of pre-mRNA splicing.

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