Publication Date:
2013-01-29
Description:
The active centre of the spliceosome consists of an intricate network formed by U5, U2 and U6 small nuclear RNAs, and a pre-messenger-RNA substrate. Prp8, a component of the U5 small nuclear ribonucleoprotein particle, crosslinks extensively with this RNA catalytic core. Here we present the crystal structure of yeast Prp8 (residues 885-2413) in complex with Aar2, a U5 small nuclear ribonucleoprotein particle assembly factor. The structure reveals tightly associated domains of Prp8 resembling a bacterial group II intron reverse transcriptase and a type II restriction endonuclease. Suppressors of splice-site mutations, and an intron branch-point crosslink, map to a large cavity formed by the reverse transcriptase thumb, and the endonuclease-like and RNaseH-like domains. This cavity is large enough to accommodate the catalytic core of group II intron RNA. The structure provides crucial insights into the architecture of the spliceosome active site, and reinforces the notion that nuclear pre-mRNA splicing and group II intron splicing have a common origin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672837/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672837/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galej, Wojciech P -- Oubridge, Chris -- Newman, Andrew J -- Nagai, Kiyoshi -- MC_U105184330/Medical Research Council/United Kingdom -- U.1051.04.016(78933)/Medical Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Jan 31;493(7434):638-43. doi: 10.1038/nature11843. Epub 2013 Jan 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23354046" target="_blank"〉PubMed〈/a〉
Keywords:
Catalytic Domain
;
*Models, Molecular
;
Nuclear Proteins/chemistry/metabolism
;
Protein Structure, Tertiary
;
Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry/genetics
;
Ribonucleoprotein, U5 Small Nuclear/*chemistry/genetics
;
Saccharomyces cerevisiae/*chemistry/genetics
;
Saccharomyces cerevisiae Proteins/*chemistry/genetics/metabolism
;
Spliceosomes/*chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
