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Publication Abstract from PubMed

Prp3 is an essential U4/U6 di-snRNP-associated protein whose functions and molecular mechanisms in pre-mRNA splicing are presently poorly understood. We show by structural and biochemical analyses that Prp3 contains a bipartite U4/U6 di-snRNA-binding region comprising an expanded ferredoxin-like fold, which recognizes a 3'-overhang of U6 snRNA, and a preceding peptide, which binds U4/U6 stem II. Phylogenetic analyses revealed that the single-stranded RNA-binding domain is exclusively found in Prp3 orthologs, thus qualifying as a spliceosome-specific RNA interaction module. The composite double-stranded/single-stranded RNA-binding region assembles cooperatively with Snu13 and Prp31 on U4/U6 di-snRNAs and inhibits Brr2-mediated U4/U6 di-snRNA unwinding in vitro. RNP-disrupting mutations in Prp3 lead to U4/U6*U5 tri-snRNP assembly and splicing defects in vivo. Our results reveal how Prp3 acts as an important bridge between U4/U6 and U5 in the tri-snRNP and comparison with a Prp24-U6 snRNA recycling complex suggests how Prp3 may be involved in U4/U6 re-assembly after splicing.

A composite double-/single-stranded RNA-binding region in protein Prp3 supports tri-snRNP stability and splicing.,Liu S, Mozaffari-Jovin S, Wollenhaupt J, Santos KF, Theuser M, Dunin-Horkawicz S, Fabrizio P, Bujnicki JM, Luhrmann R, Wahl MC Elife. 2015 Jul 10;4. doi: 10.7554/eLife.07320. PMID:26161500^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.