Brr2p-mediated unwinding of U4/U6 is promoted by a mutually exclusive intra-molecular stem loop in U4 and involves destabilization of the 5' stem-loop of U4.

ABSTRACT: Before the spliceosome engages a pre-mRNA to excise its introns, the catalytic small nuclear RNA (snRNA) U6 is inactive because of base pairing with U4 snRNA; thus, spliceosome activation requires unwinding of base paired U4/U6, composed of stem I and stem II. The Ski2-like ATPase and RNA helicase Brr2p facilitates U4/U6 unwinding and the ultimately irreversible release of U4; however, the molecular mechanism behind Brr2p-mediated U4/U6 unwinding and the roles of the snRNAs in unwinding remains incompletely understood. To investigate the mechanism in vivo in budding yeast, we screened an unwinding deficient, cold-sensitive brr2 mutant, associated with retinitis pigmentosa in humans, for genetic interactions with mutations in U4 snRNA. Destabilizing U4 mutations in either stem I or s

SUBMITTER: Nielsen KH 

PROVIDER: S-EPMC12324492 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature