Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing.
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.
Webby
Celia J
CJ
Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, Oxon OX1 3TA, UK.
Wolf
Alexander
A
Gromak
Natalia
N
Dreger
Mathias
M
Kramer
Holger
H
Kessler
Benedikt
B
Nielsen
Michael L
ML
Schmitz
Corinna
C
Butler
Danica S
DS
Yates
John R
JR
Delahunty
Claire M
CM
Hahn
Phillip
P
Lengeling
Andreas
A
Mann
Matthias
M
Proudfoot
Nicholas J
NJ
Schofield
Christopher J
CJ
Böttger
Angelika
A
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
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