EBVのノンコーディングRNAは新生RNAと結合し,宿主PAX5をウイルスのDNAに駆動する
Nara Lee1, Walter N Moss1, Therese A Yario1
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Cell
|February 10, 2015
まとめ
エプスタイン・バーウイルスのEBER2RNAはPAX5転写因子をウイルスのDNAに誘導する. この相互作用は,ウイルスの遺伝子発現と複製を調節するために極めて重要であり,ノンコーディングRNAの新たな機能を明らかにしています.
科学分野:
- 分子ウイルス学 分子ウイルス学
- エピジェネティクス エピジェネティクス
- ノンコーディングRNA 生物学
背景:
- エプスタイン・バーウイルス (EBV) は,豊富な核非コーディングRNA,EBER2.2を発現します.
- EBER2の機能と宿主細胞核内の局所化は,以前は不明でした.
- EBVゲノムの末端の繰り返し (TRs) は,重要な規制領域である.
研究 の 目的:
- EBV EBER2 RNAのクロマチンの局所化を調査する.
- EBER2と転写因子PAX5.5の機能的相互作用を解明する.
- EBER2-PAX5相互作用がEBV遺伝子調節と複製における役割を理解する.
主な方法:
- クロマチン,RNA,および温度感受性免疫降水 (CHART) を用いて,EBER2のゲノム位置を決定する.
- EBER2-PAX5の相互作用を確認するためのRNA免疫プレシピテーション (RIP).
- ウイルスの遺伝子発現と複製に対するEBER2ノックダウンの機能的影響を評価するためのRNA干渉 (RNAi).
- ベースペアリング相互作用のためのTRロカスからの新生トランスクリプトの分析.
主要な成果:
- CHARTは,EBER2がEBV TRsに局所化し,PAX5結合部位が重なり合っていることを明らかにしました.
- EBER2はPAX5と直接相互作用し,TRsへのレクルートに不可欠です.
- EBER2のノックダウンはPAX5の減退を模倣し,LMP2A/BとLMP1の発現を向上させ,リティック複製を低下させます.
- 募集は,進化的に保存されたメカニズムである新生TRトランスクリプトとのEBER2塩基配列によって媒介されます.
結論:
- EBER2は,EBV TRsにPAX5を勧誘するために,新生RNAとのベースペアリングを使用して,支架として作用します.
- この新しいRNA誘導メカニズムは,鍵となるEBVの潜在的およびリティック遺伝子を調節する.
- この発見は,DNA標的への転写因子を誘導するトランス作用非コーディングRNAの以前に説明されていない機能を明らかにしています.
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