NORAD誘発のPumilio相分離は,ゲノム安定のために必要である
Mahmoud M Elguindy1,2, Joshua T Mendell3,4,5,6
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|June 10, 2021
まとめ
長い非コーディングRNAのNORADは,相分離を使用してPumilioタンパク質を阻害し,ゲノムの安定性を維持します. このRNAによるプロセスの破壊は ゲノムの不安定性を引き起こし 細胞の調節における 重要な役割を強調します
科学分野:
- 細胞生物学
- 分子生物学
- 遺伝学
背景:
- 液体-液体相分離が 細胞組織を動かす
- RNAの代謝は相分離したRNA凝縮物によって影響を受けます.
- 特定のRNAがRNA結合タンパク質 (RBPs) を相分離によって調節するメカニズムは不明である.
研究 の 目的:
- RBPの活性を調節するRNA駆動の相分離を調査する.
- プミリオ (PUM) タンパク質の制御における長い非コーディングRNA (lncRNA) NORADの役割を決定する.
- ゲノム安定性を維持するNORAD媒介の相分離の機能を明らかにする.
主な方法:
- 哺乳類の細胞における PUM タンパク質との相互作用を研究した.
- NORADによって核化されたPUM凝縮物 (NP体) の形成を調査した.
- PUM活動とゲノム安定性に対するNORAD駆動の相分離を妨害する影響を評価した.
- PUMコンデンサートを誘導してゲノム不安定性を救うために合成RNAを使用した.
主要な成果:
- NORADは,相分離されたPUM凝縮物 (NP体) を核化することによって,PUMタンパク質を競争的に抑制する.
- 多価PUM-NORADとPUM-PUMの相互作用により,NORADは大量のPUMを隔離することができる.
- NORADによる相分離の障害は,PUM過活性化とゲノム不安定化を引き起こす.
- PUMコンデンサート形成を誘導する合成RNAは ゲノム不安定を救います
結論:
- RNA主導の相分離は,lncRNA媒介のRBP調節のための重要なメカニズムである.
- NORADはPUM活動を制御し ゲノムの安定性を維持するために 段階分離を使用します
- 段階分離は,重複的な配列要素のために潜在的に広範囲に広がるlncRNAsの重要な規制メカニズムです.
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