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Science 30 June 2006:
Vol. 312. no. 5782, pp. 1961 - 1965
DOI: 10.1126/science.1128659
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Reports

Intron Removal Requires Proofreading of U2AF/3' Splice Site Recognition by DEK

Luis Miguel Mendes Soares,1 Katia Zanier,4 Cameron Mackereth,4 Michael Sattler,4 Juan Valcárcel1,2,3*

Discrimination between splice sites and similar, nonsplice sequences is essential for correct intron removal and messenger RNA formation in eukaryotes. The 65- and 35-kD subunits of the splicing factor U2AF, U2AF65 and U2AF35, recognize, respectively, the pyrimidine-rich tract and the conserved terminal AG present at metazoan 3' splice sites. We report that DEK, a chromatin- and RNA-associated protein mutated or overexpressed in certain cancers, enforces 3' splice site discrimination by U2AF. DEK phosphorylated at serines 19 and 32 associates with U2AF35, facilitates the U2AF35-AG interaction and prevents binding of U2AF65 to pyrimidine tracts not followed by AG. DEK and its phosphorylation are required for intron removal, but not for splicing complex assembly, which indicates that proofreading of early 3' splice site recognition influences catalytic 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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