title: Jumonji domain containing protein 6 (Jmjd6) modulates splicing and specifically interacts with arginine-serine-rich (RS) domains of SR- and SR-like proteins.
abstract: The Fe(II) and 2-oxoglutarate dependent oxygenase Jmjd6 has been shown to hydroxylate lysine residues in the essential splice factor U2 auxiliary factor 65 kDa subunit (U2AF65) and to act as a modulator of alternative splicing. We describe further evidence for the role of Jmjd6 in the regulation of pre-mRNA processing including interactions of Jmjd6 with multiple arginine-serine-rich (RS)-domains of SR- and SR-related proteins including U2AF65, Luc7-like protein 3 (Luc7L3), SRSF11 and Acinus S', but not with the bona fide RS-domain of SRSF1. The identified Jmjd6 target proteins are involved in different mRNA processing steps and play roles in exon dependent alternative splicing and exon definition. Moreover, we show that Jmjd6 modifies splicing of a constitutive splice reporter, binds RNA derived from the reporter plasmid and punctually co-localises with nascent RNA. We propose that Jmjd6 exerts its splice modulatory function by interacting with specific SR-related proteins during splicing in a RNA dependent manner.
authors.affiliation: Department of Biology II, Ludwig Maximilians University, Munich, Großhaderner Strasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Heim
authors.affiliation: Department of Biology II, Ludwig Maximilians University, Munich, Großhaderner Strasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Grimm
authors.affiliation: Department of Biology II, Ludwig Maximilians University, Munich, Großhaderner Strasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Müller
authors.affiliation: Department of Biology II, Ludwig Maximilians University, Munich, Großhaderner Strasse 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Häußler
authors.affiliation: Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK Research Unit Protein Science, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Mukram M
authors.initials: MM
authors.lastname: Mackeen
authors.affiliation: Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl
authors.affiliation: Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.affiliation: School of Chemical Science, Faculty of Science and Technology, and Institute of Systems Biology (INBIOSIS) Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor Darul Ehsan, Malaysia.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
authors.affiliation: Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany boettger@zi.biologie.uni-muenchen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wolf
authors.affiliation: Department of Biology II, Ludwig Maximilians University, Munich, Großhaderner Strasse 2, 82152 Planegg-Martinsried, Germany boettger@zi.biologie.uni-muenchen.de.
authors.forename: Angelika
authors.initials: A
authors.lastname: Böttger
mesh_terms: D017398:Alternative Splicing; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D000072668:Splicing Factor U2AF
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C000607494:U2AF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D012313:RNA; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases