A composite double-/single-stranded rna-binding region in protein Prp3 supports tri-snRNP stability and splicing
Authors:
- Sunbin Liu,
- Sina Mozaffari-Jovin,
- Jan Wollenhaupt,
- Karine F. Santos,
- Matthias Theuser,
- Stanislaw Dunin-Horkawicz,
- Patrizia Fabrizio,
- Janusz Marek Bujnicki,
- Reinhard Lührmann,
- Markus C. Wahl
Abstract
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 egion 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 cts 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 reassembly after splicing.
- Record ID
- UAM8c5e334019d64c3aad6c7541147cc9ff
- Author
- Journal series
- eLife, ISSN 2050-084X
- Issue year
- 2015
- Vol
- 4
- ASJC Classification
- ; ; ;
- DOI
- DOI:10.7554/eLife.07320 Opening in a new tab
- Language
- (en) English
- Score (nominal)
- 45
- Score source
- journalList
- Score
- Publication indicators
- = 18; = 65; : 2015 = 1.671; : 2015 (2 years) = 8.282 - 2015 (5 years) =8.512
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- Uniform Resource Identifier
- https://researchportal.amu.edu.pl/info/article/UAM8c5e334019d64c3aad6c7541147cc9ff/
- URN
urn:amu-prod:UAM8c5e334019d64c3aad6c7541147cc9ff
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or PerishOpening in a new tab system.