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    We determined that over 40 spliceosomal proteins are conserved between many fungal species and humans but were lost during the evolution of S. cerevisiae, an intron-poor yeast with unusually rigid splicing signals. We analyzed null mutations in a subset of these factors, most of which had not been investigated previously, in the intron-rich yeast Cryptococcus neoformans. We found they govern splicing efficiency of introns with divergent spacing between intron elements. Importantly, most of these factors also suppress usage of weak nearby cryptic/alternative splice sites. Among these, orthologs of GPATCH1 and the helicase DHX35 display correlated functional signatures and copurify with each other as well as components of catalytically active spliceosomes, identifying a conserved G patch/helicase pair that promotes splicing fidelity. We propose that a significant fraction of spliceosomal proteins in humans and most eukaryotes are involved in limiting splicing errors, potentially through kinetic proofreading mechanisms, thereby enabling greater intron diversity. Copyright © 2021 Elsevier Inc. All rights reserved.


    Jade Sales-Lee, Daniela S Perry, Bradley A Bowser, Jolene K Diedrich, Beiduo Rao, Irene Beusch, John R Yates, Scott W Roy, Hiten D Madhani. Coupling of spliceosome complexity to intron diversity. Current biology : CB. 2021 Nov 22;31(22):4898-4910.e4

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    PMID: 34555349

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