RNA Splicing by the Spliceosome
Annual Review of Biochemistry
Vol. 89:- (Volume publication date June 2020)
Review in Advance first posted online on December 3, 2019. (Changes may still occur before final publication.)
Max E. Wilkinson,* Clément Charenton,* and Kiyoshi Nagai*
MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; email: mwilkin@mrc-lmb.cam.ac.uk, ccharent@mrc-lmb.cam.ac.uk
*All authors contributed equally to this article. M.E. Wilkinson and C. Charenton would like to dedicate this review to the memory of Kiyoshi Nagai (1949–2019)
Source/Fonte: Chemistry World
Abstract
The spliceosome removes introns from messenger RNA precursors (pre-mRNA). Decades of biochemistry and genetics combined with recent structural studies of the spliceosome have produced a detailed view of the mechanism of splicing. In this review, we aim to make this mechanism understandable and provide several videos of the spliceosome in action to illustrate the intricate choreography of splicing. The U1 and U2 small nuclear ribonucleoproteins (snRNPs) mark an intron and recruit the U4/U6.U5 tri-snRNP. Transfer of the 5′ splice site (5′SS) from U1 to U6 snRNA triggers unwinding of U6 snRNA from U4 snRNA. U6 folds with U2 snRNA into an RNA-based active site that positions the 5′SS at two catalytic metal ions. The branch point (BP) adenosine attacks the 5′SS, producing a free 5′ exon. Removal of the BP adenosine from the active site allows the 3′SS to bind, so that the 5′ exon attacks the 3′SS to produce mature mRNA and an excised lariat intron.
Expected final online publication date for the Annual Review of Biochemistry, Volume 89 is June 22, 2020. Please see
http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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