HIV-1 RNA 運命の転写開始部位制御の構造的基礎
Joshua D Brown1, Siarhei Kharytonchyk2, Issac Chaudry1
1Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Science (New York, N.Y.)
|April 25, 2020
まとめ
HIV-1 RNAキャップの5'-グアノシンの数は,その運命を決定する. 単一のグアノシン (Cap1G) はキャップを隔離する構造を形成し,2つまたは3つのグアノシン (Cap2G/Cap3G) は翻訳のためにそれを暴露する.
科学分野:
- 分子生物学
- ウイルス学
- 構造生物学
背景:
- HIV-1の遺伝子発現には,異質な5'-キャップRNAが含まれています.
- これらのRNAは,5'-グアノシン (Cap1G,Cap2G,Cap3G) の数によって異なる.
- 5'-グアノシンの数は,RNAの運命:ゲノム包装またはmRNA翻訳に影響を与える.
研究 の 目的:
- 5'-グアノシンの数がHIV-1リーダーRNAの構造と運命をどのように影響するかを調査する.
- 差異的RNA処理の基礎にある構造的メカニズムを解明する.
主な方法:
- デュテリウムで編集された核磁気共振 (NMR) スペクトロスコーピー.
- HIV-1リーダーRNAの構造探査
主要な成果:
- Cap1Gのトランスクリプトは2次元の多毛糸構造を採用し,キャップを隔離し,翻訳開始因子4Eの結合を阻害する.
- Cap2GとCap3Gのトランスクリプトは,露出したキャップとスプライスドナー残基を持つ代替構造を採用します.
- G-Cベースペアのエネルギーコストを含む構造改造は,Cap1GとCap2G/Cap3Gの構造を区別する.
結論:
- 5'-グアノシンの数はHIV-1 RNAの構造を大幅に変化させます.
- 構造的な変化はRNAの運命を決定し,mRNAの翻訳に対してゲノム包装に影響を与えます
- 単一の5'-グアノシン変異は,大きなウイルスRNAトランスクリプトの機能的分岐を誘発する.
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