Progression Through the Spliceosome Cycle Requires Prp38p Function for U4/U6 SnRNA Dissociation

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1998 Jun 10

PMID 9582287

Citations 38

Authors

J Xie

K Beickman

E Otte

B C Rymond

Affiliations

Soon will be listed here.

Abstract

The elaborate and energy-intensive spliceosome assembly pathway belies the seemingly simple chemistry of pre-mRNA splicing. Prp38p was previously identified as a protein required in vivo and in vitro for the first pre-mRNA cleavage reaction catalyzed by the spliceosome. Here we show that Prp38p is a unique component of the U4/U6.U5 tri-small nuclear ribonucleoprotein (snRNP) particle and is necessary for an essential step late in spliceosome maturation. Without Prp38p activity spliceosomes form, but arrest in a catalytically impaired state. Functional spliceosomes shed U4 snRNA before 5' splice-site cleavage. In contrast, Prp38p-defective spliceosomes retain U4 snRNA bound to its U6 snRNA base-pairing partner. Prp38p is the first tri-snRNP-specific protein shown to be dispensable for assembly, but required for conformational changes which lead to catalytic activation of the spliceosome.

Citing Articles

Dynamics and evolutionary conservation of B complex protein recruitment during spliceosome activation.

Fu X, Hoskins A Nucleic Acids Res. 2025; 53(4).

PMID: 39995036 PMC: 11850228. DOI: 10.1093/nar/gkaf124.

Dynamics and Evolutionary Conservation of B Complex Protein Recruitment During Spliceosome Activation.

Fu X, Hoskins A bioRxiv. 2024; .

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Spliceosome assembly and regulation: insights from analysis of highly reduced spliceosomes.

Black C, Whelan T, Garside E, MacMillan A, Fast N, Rader S RNA. 2023; 29(5):531-550.

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Recruitment of a splicing factor to the nuclear lamina for its inactivation.

Vester K, Preussner M, Holton N, Feng S, Schultz C, Heyd F Commun Biol. 2022; 5(1):736.

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Smu1 and RED are required for activation of spliceosomal B complexes assembled on short introns.

Keiper S, Papasaikas P, Will C, Valcarcel J, Girard C, Luhrmann R Nat Commun. 2019; 10(1):3639.

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