Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly.

ABSTRACT: Three RNA helicases - DDX42, DDX46 and DHX15 - are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b

SUBMITTER: Yang F 

PROVIDER: S-EPMC9935549 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature