title: Progression through the spliceosome cycle requires Prp38p function for U4/U6 snRNA dissociation.
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.
authors.affiliation: T.H. Morgan School of Biological Sciences, University of Kentucky, Lexington, KY 40506-0225, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.forename: K
authors.initials: K
authors.lastname: Beickman
authors.forename: E
authors.initials: E
authors.lastname: Otte
authors.forename: B C
authors.initials: BC
authors.lastname: Rymond
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D012342:RNA, Small Nuclear; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics*; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017381:Spliceosomes
chemical_list: D005656:Fungal Proteins; C076234:PRP38 protein, S cerevisiae; D000072260:RNA Splicing Factors; D012342:RNA, Small Nuclear; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017415:Ribonucleoprotein, U5 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins