Research Article

Postcatalytic spliceosome structure reveals mechanism of 3′–splice site selection

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Science  08 Dec 2017:
Vol. 358, Issue 6368, pp. 1283-1288
DOI: 10.1126/science.aar3729

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Understanding splicing from the 3′ end

The spliceosome removes introns from eukaryotic mRNA precursors and yields mature transcripts by joining exons. Despite decades of functional studies and recent progress in understanding the spliceosome structure, the mechanism by which the 3′ splice site (SS) is recognized by the spliceosome has remained unclear. Liu et al. and Wilkinson et al. report the high-resolution cryo-electron microscopy structures of the yeast postcatalytic spliceosome. The structures reveal that the 3′SS is recognized through non-Watson-Crick base pairing with the 5′SS and the branch point, stabilized by the intron region and protein factors.

Science, this issue p. 1278, p. 1283

Abstract

Introns are removed from eukaryotic messenger RNA precursors by the spliceosome in two transesterification reactions—branching and exon ligation. The mechanism of 3′–splice site recognition during exon ligation has remained unclear. Here we present the 3.7-angstrom cryo–electron microscopy structure of the yeast P-complex spliceosome immediately after exon ligation. The 3′–splice site AG dinucleotide is recognized through non–Watson-Crick pairing with the 5′ splice site and the branch-point adenosine. After the branching reaction, protein factors work together to remodel the spliceosome and stabilize a conformation competent for 3′–splice site docking, thereby promoting exon ligation. The structure accounts for the strict conservation of the GU and AG dinucleotides at the 5′ and 3′ ends of introns and provides insight into the catalytic mechanism of exon ligation.

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