Structural highlights
Function
PRP8_YEAST Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.[1] [2] [3] [4]
Publication Abstract from PubMed
The activated spliceosome (Bact) is in a catalytically inactive state and is remodeled into a catalytically active machine by the RNA helicase Prp2, but the mechanism is unclear. Here we describe a 3D electron cryomicroscopy structure of the S. cerevisiae Bact complex at 5.8 A resolution. Our model reveals that in Bact the catalytic U2/U6 RNA-Prp8 ribonucleoprotein core is already established, and the 5' splice site (ss) is oriented for step 1 catalysis but occluded by protein. The first step nucleophile - the branchsite adenosine - is sequestered within the Hsh155 HEAT domain and is held 50 A away from the 5'ss. Our structure suggests that Prp2 ATPase-mediated remodeling leads to conformational changes in Hsh155's HEAT domain that liberate the first step reactants for catalysis.
Molecular architecture of the Saccharomyces cerevisiae activated spliceosome.,Rauhut R, Fabrizio P, Dybkov O, Hartmuth K, Pena V, Chari A, Kumar V, Lee CT, Urlaub H, Kastner B, Stark H, Luhrmann R Science. 2016 Aug 25. pii: aag1906. PMID:27562955[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jackson SP, Lossky M, Beggs JD. Cloning of the RNA8 gene of Saccharomyces cerevisiae, detection of the RNA8 protein, and demonstration that it is essential for nuclear pre-mRNA splicing. Mol Cell Biol. 1988 Mar;8(3):1067-75. PMID:2835658
- ↑ Abovich N, Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997 May 2;89(3):403-12. PMID:9150140
- ↑ McPheeters DS, Muhlenkamp P. Spatial organization of protein-RNA interactions in the branch site-3' splice site region during pre-mRNA splicing in yeast. Mol Cell Biol. 2003 Jun;23(12):4174-86. PMID:12773561
- ↑ Yang K, Zhang L, Xu T, Heroux A, Zhao R. Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13817-22. Epub 2008 Sep 8. PMID:18779563
- ↑ Rauhut R, Fabrizio P, Dybkov O, Hartmuth K, Pena V, Chari A, Kumar V, Lee CT, Urlaub H, Kastner B, Stark H, Luhrmann R. Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science. 2016 Aug 25. pii: aag1906. PMID:27562955 doi:http://dx.doi.org/10.1126/science.aag1906
