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Intron Removal Requires Proofreading of U2AF/3' Splice Site Recognition by DEK
Luis Miguel Mendes Soares,1Katia Zanier,4Cameron Mackereth,4Michael Sattler,4Juan Valcárcel1,2,3*
Discrimination between splice sites and similar, nonsplice sequencesis essential for correct intron removal and messenger RNA formationin eukaryotes. The 65- and 35-kD subunits of the splicing factorU2AF, U2AF65 and U2AF35, recognize, respectively, the pyrimidine-richtract and the conserved terminal AG present at metazoan 3' splicesites. We report that DEK, a chromatin- and RNA-associated proteinmutated or overexpressed in certain cancers, enforces 3' splicesite discrimination by U2AF. DEK phosphorylated at serines 19and 32 associates with U2AF35, facilitates the U2AF35-AG interactionand prevents binding of U2AF65 to pyrimidine tracts not followedby AG. DEK and its phosphorylation are required for intron removal,but not for splicing complex assembly, which indicates thatproofreading of early 3' splice site recognition influencescatalytic activation of the spliceosome.
1 Centre de Regulació Genòmica, Passeig Marítim 37-49, 08003 Barcelona, Spain. 2 Institució Catalana de Recerca i Estudis Avançats, Passeig Marítim 37-49, 08003 Barcelona, Spain. 3 Universitat Pompeu Fabra, Passeig Marítim 37-49, 08003 Barcelona, Spain. 4 European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
* To whom correspondence should be addressed. E-mail: juan.valcarcel{at}crg.es
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