異常なRNA要素によってc-srcニューロン固有のスプライシングの活性化 in vivoおよびin vitro
1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.
Cell
|May 29, 1992
まとめ
保存されたRNA配列がマウスのc-src N1エクソンのニューロン固有のスプライシングを制御する. このアクティベーター配列は,神経細胞における正しい遺伝子発現に不可欠です.
科学分野:
- 分子生物学は分子生物学である.
- RNA スプライシング
- 遺伝子規制 遺伝子規制
背景:
- マウスのc-src遺伝子は,ニューロン特異的な代替スプライシングを受けます.
- 代替スプライシングの規制メカニズムの理解は,細胞タイプの特定の遺伝子発現に不可欠です.
研究 の 目的:
- ネズミのc-src N1exonのニューロン固有のスプライシングに関与する規制配列を特定し,特徴づけること.
- 保存された陽性作用RNA配列がSRCスプライシングパターンを調節する役割を調査する.
主な方法:
- HeLaおよびWeri-1細胞抽出物を用いたインビトロスプライシングアッセイ.
- RNAの操作により,イントロンの長さを変化させ,スプライシング依存性を評価する.
- 活性化配列を含む合成RNAを用いた阻害アッセイ.
主要な成果:
- N1エクソンのドナー部位の近くのイントロンに位置する保存された陽性作用RNA配列は,N1エクソンのニューロン固有のスプライシングに不可欠です.
- 下流イントロンの短縮により,構成エクソン4のスプライシングは,このアクティベーター配列に依存するようになった.
- In vitro再構成では,HeLa細胞はN1エクソンをスキップし,Weri-1細胞はN1エクソンを含んでいるが,両方のパターンはアクティベーターに依存していることが示された.
- アクティベーター配列の合成RNA断片は,両方のスプライシングパターンを阻害し,結合因子の関与を示唆した.
結論:
- 特定されたRNA配列は,ニューロン特異的なc-src N1エクソン含有のための重要な調節器として作用します.
- このメカニズムは,タンパク質因子の配列特異的結合をアクティベーターRNAに伴う.
- この調節要素は,c-src遺伝子からニューロンのトランスクリプトの多様性を生み出す上で重要な役割を果たします.
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