RNA Splicing by the Spliceosome

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 provi...

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Veröffentlicht in:Annual review of biochemistry 2020-06, Vol.89 (1), p.359-388
Hauptverfasser: Wilkinson, Max E, Charenton, Clément, Nagai, Kiyoshi
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creator Wilkinson, Max E
Charenton, Clément
Nagai, Kiyoshi
description 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.
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subjects Adenosine
cryo-electron microscopy
cryo-EM
crystallography
Genetics
helicases
Introns
Metal ions
mRNA
pre-mRNA splicing
Ribonucleoproteins
Ribonucleoproteins (small nuclear)
RNA catalysis
snRNA
spliceosome
Splicing
Unwinding
title RNA Splicing by the Spliceosome
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