Molecular Mechanisms of pre-mRNA Splicing through Structural Biology of the Spliceosome.

Chuangye Yan, Ruixue Wan, Yigong Shi

Cold Spring Harbor perspectives in biology 2019 Jan 02

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Precursor messenger RNA (pre-mRNA) splicing is executed by the spliceosome. In the past 3 years, cryoelectron microscopy (cryo-EM) structures have been elucidated for a majority of the yeast spliceosomal complexes and for a few human spliceosomes. During the splicing reaction, the dynamic spliceosome has an immobile core of about 20 protein and RNA components, which are organized around a conserved splicing active site. The divalent metal ions, coordinated by U6 small nuclear RNA (snRNA), catalyze the branching reaction and exon ligation. The spliceosome also contains a mobile but compositionally stable group of about 13 proteins and a portion of U2 snRNA, which facilitate substrate delivery into the splicing active site. The spliceosomal transitions are driven by the RNA-dependent ATPase/helicases, resulting in the recruitment and dissociation of specific splicing factors that enable the reaction. In summary, the spliceosome is a protein-directed metalloribozyme. Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.

Citation

Chuangye Yan, Ruixue Wan, Yigong Shi. Molecular Mechanisms of pre-mRNA Splicing through Structural Biology of the Spliceosome. Cold Spring Harbor perspectives in biology. 2019 Jan 02;11(1)