Xist局所化と遺伝子静止を媒介するタンパク質アセンブリ

Amy Pandya-Jones¹, Yolanda Markaki^1,2, Jacques Serizay^1,3,4

¹Department of Biological Chemistry at the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Nature

|September 10, 2020

まとめ

長い非コーディングRNAのXistは,X染色体不活性化 (XCI) と遺伝性遺伝子静止に不可欠なタンパク質濃縮物を種にし,Xist独立相に移行する.

科学分野:

分子生物学
エピジェネティクス
ゲノミクス

背景:

核の区間は,よく理解されていない分子力によって遺伝子発現を制御します.
長い非コーディングRNAのXistは,X染色体不活性化 (XCI) のコンパートメントを形成するためにタンパク質を勧誘する.
不活性なX (Xi) コンパートメントは,安定したXist独立状態に移行する.

研究の目的:

Xist媒介によるコンパートメント形成と遺伝性遺伝子静止の基礎となる分子機構を調査する.
タンパク質の構成要素とXi区画の安定性を左右する力を特定する.
XIS-インデペンデントのXCIへの移行を理解する.

主な方法:

タンパク質とRNAの相互作用を研究する生化学分析
細胞画像でコンパートメントの形成と動態を視覚化します
XCIで特定されたタンパク質の機能を評価するための遺伝子操作.

主要な成果:

XistのRNA結合タンパク質 (PTBP1,MATR3,TDP-43,CELF1) は,XistのE-リピート要素に組み込まれている.
これらのタンパク質は遺伝子の静止とXISTの固定に不可欠な自己集積コンデンサートを形成します
凝縮物はXistから独立して遺伝子サイレンスを維持し,Xistから独立したXCIフェーズに不可欠です.

結論:

Xistは,どこにでも存在するRNA結合タンパク質の凝縮液を蒔き,Xiコンパートメントを開始します.
このコンデンサートは遺伝性遺伝子静止を駆動し,XIS-独立のXCIへの移行を支えている.
RNAテンプレートによるタンパク質の集積による遺伝的記憶の新たなメカニズムを明らかにした.

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