title: Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing.
abstract: The finding that the metazoan hypoxic response is regulated by oxygen-dependent posttranslational hydroxylations, which regulate the activity and lifetime of hypoxia-inducible factor (HIF), has raised the question of whether other hydroxylases are involved in the regulation of gene expression. We reveal that the splicing factor U2 small nuclear ribonucleoprotein auxiliary factor 65-kilodalton subunit (U2AF65) undergoes posttranslational lysyl-5-hydroxylation catalyzed by the Fe(II) and 2-oxoglutarate-dependent dioxygenase Jumonji domain-6 protein (Jmjd6). Jmjd6 is a nuclear protein that has an important role in vertebrate development and is a human homolog of the HIF asparaginyl-hydroxylase. Jmjd6 is shown to change alternative RNA splicing of some, but not all, of the endogenous and reporter genes, supporting a specific role for Jmjd6 in the regulation of RNA splicing.
authors: Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, Oxon OX1 3TA, UK.
authors: Celia J
authors: CJ
authors: Webby
authors: Alexander
authors: A
authors: Wolf
authors: Natalia
authors: N
authors: Gromak
authors: Mathias
authors: M
authors: Dreger
authors: Holger
authors: H
authors: Kramer
authors: Benedikt
authors: B
authors: Kessler
authors: Michael L
authors: ML
authors: Nielsen
authors: Corinna
authors: C
authors: Schmitz
authors: Danica S
authors: DS
authors: Butler
authors: John R
authors: JR
authors: Yates
authors: Claire M
authors: CM
authors: Delahunty
authors: Phillip
authors: P
authors: Hahn
authors: Andreas
authors: A
authors: Lengeling
authors: Matthias
authors: M
authors: Mann
authors: Nicholas J
authors: NJ
authors: Proudfoot
authors: Christopher J
authors: CJ
authors: Schofield
authors: Angelika
authors: A
authors: Böttger
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D055162:Biocatalysis; D002460:Cell Line; D002853:Chromatography, Liquid; D006367:HeLa Cells; D006801:Humans; D006900:Hydroxylation; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D000072668:Splicing Factor U2AF; D053719:Tandem Mass Spectrometry; D014335:Tropomyosin / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; D014335:Tropomyosin; C000607494:U2AF2 protein, human; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine