Journal
ANNUAL REVIEW OF BIOPHYSICS, VOL 47
Volume 47, Issue -, Pages 175-199Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-biophys-070317-033410
Keywords
structural biology; electron microscopy; RNA-protein complexes; spliceosome
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Funding
- MRC [MC_U105184330] Funding Source: UKRI
- Medical Research Council [MC_U105184330] Funding Source: Medline
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The removal of noncoding introns from pre-messenger RNA(pre-mRNA) is an essential step in eukaryotic gene expression and is catalyzed by a dynamic multi-megadalton ribonucleoprotein complex called the spliceosome. The spliceosome assembles on pre-mRNA substrates by the stepwise addition of small nuclear ribonucleoprotein particles and numerous protein factors. Extensive remodeling is required to form the RNA-based active site and to mediate the pre-mRNA branching and ligation reactions. In the past two years, cryo-electron microscopy (cryo-EM) structures of spliceosomes captured in different assembly and catalytic states have greatly advanced our understanding of its mechanism. This was made possible by long-standing efforts in the purification of spliceosome intermediates as well as recent developments in cryo-EM imaging and computational methodology. The resulting high-resolution densities allow for de novo model building in core regions of the complexes. In peripheral and less ordered regions, the combination of cross-linking, bioinformatics, biochemical, and genetic data is essential for accurate modeling. Here, we summarize these achievements and highlight the critical steps in obtaining near-atomic resolution structures of the spliceosome.
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