ADAR1によるRNA編集は,MDA5が内生的なdsRNAを非自己として感知することを防ぐ

Brian J Liddicoat¹, Robert Piskol², Alistair M Chalk¹

¹St. Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia. Department of Medicine, St. Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.

Science (New York, N.Y.)

|August 15, 2015

まとめ

ADAR1によるアデノシンからイノシンへの編集は,胚の死亡を防ぐために不可欠です. このRNA編集は,内生トランスクリプトによる二重鎖RNA (dsRNA) 感知経路の活性化を防ぐ.

科学分野:

分子生物学
遺伝学
免疫学

背景:

アデノシンからイノシン (A-to-I) 編集は,重要なRNA改変である.
ADAR (RNAに作用するアデノシン・デアミナーゼ) 酵素は,AからIの編集を媒介する.
ADAR1はRNA編集以上の機能を提案しています.

研究の目的:

ADAR1媒介によるRNA編集の重要な役割を明らかにする.
ADAR1の in vivo 基質と機能を調査する.
ADAR1の重要な機能が RNA編集であるかどうかを判断する.

主な方法:

編集欠陥ADAR1変異 (Adar1 ((E861A/E861A)) を持つマウスを生成した.
胚の死亡率とインターフェロン/dsRNA感受経路の活性化を分析した.
ADAR1基板を特定するために全ゲノム解析を行いました.
dsRNAセンサMDA5を削除することで救出フェノタイプを評価した.

主要な成果:

アダール1 ((E861A/E861A) の胚はE13.5の胚死亡率を示した.
インターフェロンとdsRNA感受経路の活性化が変異胚で観察された.
ゲノム全体の解析は,内生トランスクリプトのdsRNA幹ループのハイパー編集を明らかにした.
MDA5の救助胚死亡率とフェノタイプの同時削除

結論:

ADAR1の重要な機能は,内生的なdsRNAのA-to-I編集である.
この編集は,細胞性 dsRNA 応答の活性化を防ぐ.
ADAR1は内生的なdsRNAを編集することによって,先天的な免疫の重要な調節体として作用する.

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