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ストレスによる相分離は 適応的で進化的に調整された反応です

Joshua A Riback1, Christopher D Katanski2, Jamie L Kear-Scott2

  • 1Graduate Program in the Biophysical Sciences, University of Chicago, Chicago, IL 60673, USA.

Cell
|March 12, 2017
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まとめ

ポリA結合タンパク質 (Pab1) はストレスセンサとして作用し,生理学的ストレス下で水素ゲルを形成します. Pab1相分離に影響する変異は,長時間ストレス中に適性を低下させ,ストレス発症の検出のための一般化可能なメカニズムを明らかにします.

キーワード:
RNA結合タンパク質エネルギー枯渇熱ショック本質的に無秩序なタンパク質複雑性が低い地域膜のない器官pH値についてポリ (A) 結合タンパク質クイナリ構造ストレス・グランブル

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科学分野:

  • 細胞生物学
  • 生物化学
  • 分子生物学

背景:

  • ユカリオット細胞は,ストレス中にRNA結合タンパク質からストレス粒子を形成する.
  • インビトロ研究では,ストレスに関連したタンパク質が液体またはヒドロゲル組成を形成し,しばしば非生理学的条件を必要とします.

研究 の 目的:

  • 生理学的ストレス条件下におけるポリ・A結合タンパク質 (Pab1) の相分離行動を調査する.
  • パブ1の低複雑性領域 (LCR) とRNAの相分離における役割を決定する.
  • ストレス時の生物の適性に対するPab1相分離のインビボ関連性を評価する.

主な方法:

  • 様々なストレス条件下でのPab1のインビトロ相分離試験
  • Pab1とその変異体の生体物理的特徴
  • イーストの遺伝学とストレス反応に関する in vivo 研究
  • LCRの変異を導くための進化パターンの分析

主要な成果:

  • Pab1は,生理学的ストレスにさらされると,in vitroで相分離と水凝土形成を経験する.
  • 他のRNA結合タンパク質とは異なり,Pab1のLCRは脱混合に欠かせず,RNAは相分離を阻害する.
  • パブ1のLCRが相分離を阻害する突然変異は,長期的ストレスで酵母適性を低下させる.

結論:

  • ポリA結合タンパク質は,生理学的ストレスセンサとして機能し,ストレス発症をマークするために相分離を使用します.
  • LCRから独立し,RNAによって抑制されるPab1のユニークな相分離機構は,ストレス反応に不可欠です.
  • この段階分離によるストレス感知のメカニズムは,生物学的システム全体に広く一般化可能である.