紫外線照射は,同じ遺伝子でコードされたタンパク質に機能的に反対する非コーディングRNAを誘導する
Laura Williamson1, Marco Saponaro2, Stefan Boeing3
1Mechanisms of Transcription Laboratory, The Francis Crick Institute, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
Cell
|February 21, 2017
まとめ
紫外線照射はDNA損傷反応を誘発し,転写を遅らせ,より短いRNA同型を好む. 非コーディングASCC3RNAアイソフォームは,タンパク質をコードする形態に対抗して,転写回復に不可欠です.
科学分野:
- 分子生物学
- 遺伝学
- 生物化学
背景:
- DNA損傷反応は ゲノムの整合性を維持するのに 極めて重要です
- 転写調節は ストレスに対する細胞の反応に 重要な役割を果たします
- 代替スプライシングは,異なる機能を持つ多様なRNA同型を生成する.
研究 の 目的:
- 紫外線によるDNA損傷後の全ゲノムにわたる転写変化を調査する.
- DNA損傷反応における代替末尾エクソンの役割を解明する.
- 転写回復における異なるASCC3転写アイソフォームの機能を特徴づける.
主な方法:
- 高空間と時間解像度の全ゲノム解析
- 細胞を紫外線で照射して DNAを損傷させる
- mRNAアイソフォームシフトとその機能的役割の分析
主要な成果:
- 紫外線照射は転写の減速を引き起こし,プロモーター近接領域に遺伝子の活動を制限する.
- 代替末尾エクソン (ALE) を含むより短いmRNAアイソフォームへのシフトが観察されています.
- ALEによって生成される非コーディングASCC3RNAアイソフォームは,紫外線損傷後の転写回復に不可欠である.
- タンパク質をコードしないASCC3異形は,タンパク質をコードするASCC3異形の機能を逆転させる.
結論:
- ASCC3遺伝子は反抗的なコーディングと非コーディングのトランスクリプトイソフォームを生成する.
- これらのアイソフォームは,紫外線損傷後の転写回復を調節する上で,決定的で対極的な役割を果たします.
- 転写調節と代替スプライシングは,DNA損傷応答の重要な構成要素です.
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