Wahl, Markus C.

[["dc.bibliographiccitation.firstpage","2576"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","Genes & Development"],["dc.bibliographiccitation.lastpage","2587"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Absmeier, Eva"],["dc.contributor.author","Wollenhaupt, Jan"],["dc.contributor.author","Mozaffari-Jovin, Sina"],["dc.contributor.author","Becke, Christian"],["dc.contributor.author","Lee, Chung-Tien"],["dc.contributor.author","Preussner, Marco"],["dc.contributor.author","Heyd, Florian"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Luehrmann, Reinhard"],["dc.contributor.author","Santos, Karine F."],["dc.contributor.author","Wahl, Markus C."],["dc.date.accessioned","2018-11-07T09:47:30Z"],["dc.date.available","2018-11-07T09:47:30Z"],["dc.date.issued","2015"],["dc.description.abstract","The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an similar to 500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6.U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 disnRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation."],["dc.identifier.doi","10.1101/gad.271528.115"],["dc.identifier.isi","000366758700005"],["dc.identifier.pmid","26637280"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12754"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35127"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cold Spring Harbor Lab Press, Publications Dept"],["dc.relation.issn","1549-5477"],["dc.relation.issn","0890-9369"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]