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Coupling of spliceosome complexity to intron diversity

Authors :
Beiduo Rao
Scott William Roy
Jade Sales-Lee
Daniela S. Perry
John R. Yates
Irene Beusch
Jolene K. Diedrich
Hiten D. Madhani
Bradley A. Bowser
Source :
Curr Biol
Publication Year :
2021
Publisher :
Elsevier BV, 2021.

Abstract

SUMMARYWe 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.

Details

ISSN :
09609822
Volume :
31
Database :
OpenAIRE
Journal :
Current Biology
Accession number :
edsair.doi.dedup.....c61563bbf824602886369630fb7f561c