Structural analysis shows spliceosome-induced closure of an α-helical super-helix in the proto-oncogenic splicing factor SF3b1
Year: 2019
Type: article
Abstract: The SF3b1 splicing factor is a subunit of a multiprotein SF3b complex that is a checkpoint protein for spliceosome assembly.SF3b1 comprises a super-helix of repeating -helical units.In the context of the spliceosome, the SF3b1 -helical repeats bind a duplex between the spliceosomal U2 snRNA and the pre-mRNA branch point sequence, which ultimately offers an adenosine nucleophile for the splicing reaction.Several SF3b structures now are available, including human homologues in the isolated state, pre-B, B, or B act spliceosome assemblies 1 , and yeast homologues in the A, pre-B, B, or B act spliceosome assemblies 2 .Acquired mutations of SF3b1 commonly recur among hematologic malignancies and cancers.Active "opening" of the SF3b1 torus by ATP-dependent RNA unwindases has been proposed to load SF3b1 on the U2 -BPS duplex and alter branchpoint choice in the presence of cancer-associated mutations.Yet, whether the SF3b1 superhelix opens or closes, and the underlying structural changes, have yet to be rigorously analyzed.
Institutions: University of Rochester Medicine, University of Rochester
Language: English
Topic: RNA Research and Splicing
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2996800286