Evidence for complex dynamics during U2 snRNP selection of the intron branchpoint.

ABSTRACT: Splicing of pre-mRNA is initiated by binding of U1 to the 5' splice site and of Msl5-Mud2 heterodimer to the branch site (BS). Subsequent binding of U2 displaces Msl5-Mud2 from the BS to form the prespliceosome, a step governing branchpoint selection and hence 3' splice site choice, and linking splicing to myelodysplasia and many cancers in human. Two DEAD-box proteins, Prp5 and Sub2, are required for this step, but neither is stably associated with the pre-mRNA during the reaction. Using BS-mutated ACT1 pre-mRNA, we previously identified a splicing intermediate complex, FIC, which contains U2 and Prp5, but cannot bind the tri-snRNP. We show here that Msl5 remains associated with the upstream cryptic branch site (CBS) in the FIC, with U2 binding a few bases downstream of the BS. U2 mutants

SUBMITTER: Kao CY 

PROVIDER: S-EPMC8464032 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature