Jmjd6は,RNAスプライシングに関連するタンパク質であるU2AF65のリジル-水酸化を触媒化する
Celia J Webby1, Alexander Wolf, Natalia Gromak
1Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, Oxon OX1 3TA, UK.
Science (New York, N.Y.)
|July 4, 2009
まとめ
Jumonjiドメイン-6タンパク質 (Jmjd6) は,スプライシング因子であるU2小核リボ核タンパク質補助因子65キロダルトン亜単位 (U2AF65) を水酸化する. Jmjd6によるこの水酸化は,特に代替RNAスプライシングを調節する.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- 翻訳後の修正 翻訳後の修正
背景:
- メタゾアンの低酸素反応は,低酸素誘導因子 (HIF) の酸素依存の翻訳後の水酸化によって調節されます.
- この規制はHIFの活性と寿命に影響し,遺伝子発現制御に関与する他のヒドロキシラゼの調査を促した.
研究 の 目的:
- 翻訳後の改変と遺伝子発現の調節におけるJumonjiドメイン-6タンパク質 (Jmjd6) の役割を調査する.
- Jmjd6がHIF以外の他のタンパク質の水酸化を触媒化するかどうかを判断する.
主な方法:
- U2小核リボ核タンパク質補助因子65キロダルトンサブユニット (U2AF65) の翻訳後の改変を調査しました.
- U2AF65.65のリシル-5-ヒドロキシル化に起因する酵素を特定するために生化学的測定を用いた.
- Jmjd6の活性が内生性およびレポーター遺伝子の代替RNAスプライシングに与える影響を評価した.
主要な成果:
- 特定されたJmjd6は,U2AF65.65のリシル-5-水酸化を触媒化するFe(II) と2オキシグルタラート依存型ダイオキシゲナーゼである.
- Jmjd6は,脊椎動物の発達に役割を果たす核タンパク質であり,HIFヒドロキシル化に関与する同位体に似ていることが実証されました.
- Jmjd6が遺伝子のサブセットの代替RNAスプライシングを変化させることを示した.
結論:
- Jmjd6は,スプライシング因子U2AF65.6の翻訳後のヒドロキシル化を通じて,代替RNAスプライシングを調節する特定の役割を果たしています.
- この発見は,Jmjd6の既知の機能をHIF調節を超えて拡張し,遺伝子発現制御におけるその重要性を強調しています.
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There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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