Research ArticleStructural Biology

Structure of a yeast spliceosome at 3.6-angstrom resolution

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Science  20 Aug 2015:
DOI: 10.1126/science.aac7629

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Splicing of pre-messenger RNA (pre-mRNA) in yeast is executed by the spliceosome, which consist of five small nuclear ribonucleoprotein particles (snRNPs), nineteen complex (NTC), NTC related (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 by single particle, cryo-electron microscopy. This spliceosome contains U2 and U5 snRNPs, NTC, NTR, U6 snRNA, and an RNA intron lariat. The atomic model includes 10,574 amino acids from 37 proteins and 4 RNA molecules, with a combined molecular mass of approximately 1.3 mega-Daltons. Spp42 (Prp8 in S. cerevisiae), the key protein component of U5 snRNP, forms a central scaffold and anchors the catalytic center. Both the appearance and the placement of protein components are evolved to facilitate the dynamic process of pre-mRNA splicing. The near-atomic resolution structure of a central spliceosome provides a molecular framework for mechanistic understanding of pre-mRNA splicing.

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