ドロソフィラのA-to-Iプリ-mRNA編集は,主に成人の神経系の機能と整合性に関与しています

M J Palladino¹, L P Keegan, M A O'Connell

¹Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington 06030, USA.

Cell

|August 31, 2000

まとめ

果実ハエ (ドロソフィラ) の特定のRNA編集は,神経系の機能に極めて重要です. dADAR酵素を削除すると,深刻な行動的欠陥と神経変性が生じ,成人のハエの行動におけるその重要性を強調します.

科学分野:

分子生物学は分子生物学である.
神経科学は神経科学である.
遺伝学遺伝学とは

背景:

アデノシン-イノシン (A-to-I) RNA編集は,哺乳類を含む様々な生物に見られる転写後の改変である.
特定のA-to-IRNA編集は,ドロソフィラのイオンチャネル遺伝子のいくつかで特定されており,保存されたメカニズムを示唆しています.
ドロソフィラ・メラノガスターは,哺乳類のADARと同型であるRNA編集酵素候補であるdADARを持っています.

研究の目的:

ドロソフィラ菌におけるdADARの機能的役割を調査する.
廃止されたA-to-IRNA編集がドロソフィラの生理学と行動に与える影響を決定する.
ハエの神経系におけるdADAR媒介によるRNA編集の標的と結果を特定する.

主な方法:

ADAR活動が欠けているdADAR消去変異体の生成.
既知のターゲットのサイト固有のRNA編集の評価 (3つのイオンチャネルトランスクリプトの25サイト).
行動分析 (麻痺,移動,震) と神経変性評価を含む,dADAR変異体のフェノタイプ分析.

主要な成果:

dADAR消去変異体は,ドロソフィラの既知のサイト固有のRNA編集を完全に廃止しました.
大人のdADAR変異種は,温度感受性麻痺や調整不全を含む,重度の年齢依存の行動欠陥を示した.
dADAR変異体では神経変異が観察され,現象的重症と相関していたが,変異体は短命ではなかった.

結論:

dADARによるドロソフィラのA-to-IRNA編集は,正常な成人の神経系の機能と行動に不可欠です.
dADARによる編集の主なターゲットは,神経系にあるようです.
この研究は,神経細胞の完全性と複雑な行動を維持する上でRNA編集の重要な役割を強調しています.

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