5'非翻訳領域からの翻訳は,統合されたストレス反応を形作る
Shelley R Starck1, Jordan C Tsai2, Keling Chen3
1Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA. Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. shelley@walterlab.ucsf.edu nshastri@berkeley.edu peter@walterlab.ucsf.edu.
Science (New York, N.Y.)
|January 30, 2016
まとめ
この研究は,BiP mRNAにおける上流のオープン・リーディングフレーム (uORF) が,統合ストレス反応 (ISR) 中の翻訳を可能にすることを示している. これらのuORFは免疫系の認識のために細胞にシグナルを与えるペプチドを生成する.
科学分野:
- 分子生物学
- 免疫学
- 細胞生物学
背景:
- アノテーションされたコード配列を超えて翻訳された領域は,重要なプロテオームの構成要素です.
- 統合ストレス応答 (ISR) コントロール下でのmRNAの上流オープンリーディングフレーム (uORF) は特権翻訳を示す.
- この特権翻訳は,真核のイニシアチブ因子2-グアノシントリホスファートイニシアチブメチオニルトランスファーRNA (eIF2·GTP·Met-tRNA) の抑制にもかかわらず発生する.
研究 の 目的:
- ISR中に uORFの翻訳製品を直接測定する.
- 細胞ストレス中のBiP mRNA翻訳におけるuORFの役割を調査する.
- uORF由来ペプチドの潜在的な免疫学的影響を調査する.
主な方法:
- uORF変換を定量化するために,T細胞による翻訳を追跡する新しい方法の開発.
- BiP mRNAの5' 未翻訳領域におけるuORF翻訳イベントの分析
- BiP表現における代替開始因子eIF2Aおよび非AUG開始のuORFの要件を調査する.
主要な成果:
- BiP mRNAのuORFからAUGスタートコドンで開始されなかったシグネチャートランスレーションイベントを特定した.
- ISR中のBiP発現は,eIF2Aと非AUG発起のuORFの両方に依存していることが実証された.
- 特定のmRNAをISRから保護する様々なチャペロンに対する持続的なuORF翻訳が観察されました.
結論:
- 非AUG誘発のuORFとeIF2Aは,ISR下でBiP mRNAの翻訳に不可欠である.
- 持続的なuORF翻訳は,特定のmRNAをISR誘発の阻害から保護する可能性があります.
- uORF翻訳は,MHCクラスIリガンドとして機能するペプチドを生成し,適応性免疫認識のための細胞を潜在的にマークします.
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