Upf1は3'UTRの長さを感知して,mRNAの分解を活性化します
J Robert Hogg1, Stephen P Goff
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. jh2721@columbia.edu
Cell
|October 30, 2010
まとめ
無意味な媒介による衰退 (NMD) は,欠陥のあるmRNAを分解する. この研究は,翻訳終結効率に影響される長い3'未翻訳領域 (3'UTRs) のmRNAを分解する2段階のUpf1-依存メカニズムを明らかにしています.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- RNA 生物学 RNA 生物学
背景:
- 無意味な媒介による衰退 (NMD) は,細胞品質管理のための重要なmRNA監視経路です.
- NMDの調節不良は,様々なヒト疾患に関与しています.
- NMDにおける3'未翻訳領域 (3'UTR) 長さの役割は完全に理解されていません.
研究 の 目的:
- 長い3'UTRsによって媒介されるUpf1-依存のmRNA分解のメカニズムを解明する.
- 3'UTR長さの翻訳的な読み込みとNMDの相互作用を調査する.
- 3'UTR長さの監視のためのモデルを提案する.
主な方法:
- メッセンジャーリボヌクレオプロテインの浄化のために利用されたRNAのヘアピンタグされたmRNA.
- HIV-1 3'UTR配列を含むmRNAとUpf1の関連性を調査した.
- Upf1の募集とRNAの衰退に翻訳的な読み込みを促進するレトロウイルスRNA要素の影響を分析した.
主要な成果:
- 長い3'UTRを持つmRNAのUpf1-依存分解の2段階メカニズムを発見した.
- Upf1が3'UTRの長さに依存した方法でmRNAと結合することを示した.
- トランスレーション・リーススルーがUpf1の募集と,その後のRNAの崩壊を阻害し,3'UTRの長さの認識と崩壊の開始を分離することを示した.
結論:
- Upf1均衡結合がRNA分解への結合に先行する3'UTR長さの監視モデルを提案した.
- NMDの調節における翻訳終了効率の規制的な役割を強調した.
- 人間の健康と病気におけるmRNA品質管理経路の重要性を強調した.
関連する概念動画
Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
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Cis-acting Elements involved in mRNA stability
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
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