tRNA由来断片の偽ウリジレーションは,幹細胞における翻訳制御を誘導する

Nicola Guzzi¹, Maciej Cieśla¹, Phuong Cao Thi Ngoc¹

¹Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Faculty of Medicine, Lund University, Lund, Sweden.

Cell

|April 10, 2018

まとめ

偽ウリジレーション (Ψ) は,幹細胞の結合を調節するために,tRNA断片 (tRFs) を介して翻訳制御を指示する. この表遺伝的メカニズムは胚の発達に影響を与え,骨髄分裂症候群に関与しています.

科学分野:

エピジェネティクス
分子生物学
発達生物学

背景:

偽ウリジレーション (Ψ) は最も豊富に存在するRNAの改変であるが,その生物学的役割はほとんど不明である.
RNAの改変を理解することは遺伝子調節と細胞過程の解読に不可欠です

研究の目的:

幹細胞のコミットメントにおける偽ウリジレーションの生物学的機能を調査する.
遺伝子発現と細胞運命を影響するメカニズムを解明する.

主な方法:

偽ウリジン"ライター"酵素 PUS7の役割を調査した.
分析されたtRNA由来小断片 (tRFs) と,その翻訳開始への影響.
胚性幹細胞モデルを使用し,血液生成性幹細胞の関与を研究した.

主要な成果:

PUS7は,翻訳開始複合体をターゲットとするtRFを修正し,活性化します.
幹細胞のPUS7不活性化により,tRF媒介による翻訳制御が妨げられ,タンパク質合成が増加し,生殖層の特異性が低下する.
この経路の調節不良は造血幹細胞の結合に影響し,骨髄不全症候群と関連しています.

結論:

偽ウリジル化駆動の転写後のプログラムは,幹細胞における翻訳制御に不可欠である.
このメカニズムは初期の胚形成と幹細胞の機能に重要な役割を果たします
ミエロディスプラスティック症候群のような病気の理解と治療への影響

キーワード:

PUS7 について RNAの改変胚形成血液形成骨髄分裂症候群タンパク質合成プセウドウリジン幹細胞 tRNA 断片翻訳管理

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