Understanding the dynamic design of the spliceosome

Trends Biochem Sci. 2024 Apr 18:S0968-0004(24)00078-1. doi: 10.1016/j.tibs.2024.03.012. Online ahead of print.ABSTRACTThe spliceosome catalyzes the splicing of pre-mRNAs. Although the spliceosome evolved from a prokaryotic self-splicing intron and an associated protein, it is a vastly more complex and dynamic ribonucleoprotein (RNP) whose function requires at least eight ATPases and multiple RNA rearrangements. These features afford stepwise opportunities for multiple inspections of the intron substrate, coupled with spliceosome disassembly for substrates that fail inspection. Early work using splicing-defective pre-mRNAs or small nuclear (sn)RNAs in Saccharomyces cerevisiae demonstrated that such checks could occur in catalytically active spliceosomes. We review recent results on pre-mRNA splicing in various systems, including humans, suggesting that earlier steps in spliceosome assembly are also subject to such quality control. The inspection-rejection framework helps explain the dynamic nature of the spliceosome.PMID:38641465 | DOI:10.1016/j.tibs.2024.03.012

Source: Trends in Biochemical Sciences - April 19, 2024 Category: Biochemistry Authors: Irene Beusch Hiten D Madhani Source Type: research