Jmjd6 Catalyses Lysyl-Hydroxylation of U2AF65, a Protein Associated with RNA Splicing

被引：310

作者：

Webby, Celia J. ^{[1
,2
]}

Wolf, Alexander ^{[3
]}

Gromak, Natalia ^{[4
]}

Dreger, Mathias ^{[5
]}

Kramer, Holger ^{[6
]}

Kessler, Benedikt ^{[6
]}

Nielsen, Michael L. ^{[7
]}

Schmitz, Corinna ^{[3
]}

Butler, Danica S. ^{[1
,2
]}

Yates, John R., III ^{[8
]}

Delahunty, Claire M. ^{[8
]}

Hahn, Phillip ^{[9
]}

Lengeling, Andreas ^{[9
,10
,11
]}

Mann, Matthias ^{[7
]}

Proudfoot, Nicholas J. ^{[4
]}

Schofield, Christopher J. ^{[1
,2
]}

Boettger, Angelika ^{[3
]}

机构：

[1] Univ Oxford, Chem Res Lab, Oxford OX1 3TA, England

[2] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3TA, England

[3] Univ Munich, Dept Biol 2, D-82152 Planegg Martinsried, Germany

[4] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[5] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England

[6] Univ Oxford, Oxford OX3 7BN, England

[7] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[8] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[9] Helmholtz Ctr Infect Res, Res Grp Infect Genet, D-38124 Braunschweig, Germany

[10] Univ Edinburgh, Roslin Inst, EBVC, Roslin EH25 9RG, Midlothian, Scotland

[11] Univ Edinburgh, Royal Dick Sch Vet Studies, EBVC, Roslin EH25 9RG, Midlothian, Scotland

来源：

SCIENCE | 2009年 / 325卷 / 5936期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

PHOSPHATIDYLSERINE RECEPTOR; APOPTOTIC CELLS; NUCLEAR-PROTEIN; CLEARANCE;

D O I：

10.1126/science.1175865

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：90 / 93

页数：4

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