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レトロエレメントLx9は,ウイルス感染に対する免疫反応を抑制します
Nenad Bartonicek1,2, Romain Rouet1,3, Joanna Warren1
1The Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
Nature
|August 10, 2022
まとめ
Lx9c11のような 移植可能な要素は 免疫系を調節します マウスでこの元素を削除すると ウイルス感染に対する致死的な免疫過剰反応を引き起こし ホストの生存におけるその役割を強調しました
科学分野:
- ゲノミクス
- 免疫学
- 分子生物学
背景:
- 移植可能な要素 (TEs) は,哺乳類のゲノムの大部分を構成する移動性DNA配列である.
- TEs内の規制DNA要素は,遺伝子発現と細胞現象型を制御する役割を示唆しています.
- 古代の保存されたTEsは規制機能を持つ可能性が高いが,実験的検証が必要である.
研究 の 目的:
- 哺乳類の免疫反応における特定の移植可能な要素Lx9c11の調節作用を調査する.
- ウイルスの感染中に宿主生存に対するLx9c11の削除の機能的結果を決定する.
主な方法:
- マウスのLx9c11レトロトランスポゾンを削除するためにCRISPR- Cas9遺伝子編集が使用されました.
- 免疫反応と生存率を評価するために,マウスをウイルスに感染させた.
- 非コーディングRNA (Lx9c11-RegoS) の発現と,シュレーフェン族の遺伝子の調節を分析した.
主要な成果:
- Lx9c11の削除は,ウイルス感染に対する過剰で致死的な免疫反応をもたらしました.
- Lx9c11は,非コーディングRNAであるLx9c11-RegoSを生成するために不可欠です.
- Lx9c11-RegoSは,シュレファンの家族遺伝子を調節し,Lx9c11ノックアウトマウスの高炎症を緩和し,致死性を防止します.
結論:
- 移植可能な要素は免疫システムの重要な調節体として機能する.
- レトロトランスポゾンLx9c11とその由来の非コーディングRNA (Lx9c11- RegoS) は,ウイルス感染中に宿主の生存に不可欠です.
- これらの発見は,宿主の生存を促進する免疫反応を制御する移植可能な要素の役割を示しています.
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