植物のDicer-RNA複合体によるsiRNA生成のメカニズム

Qian Wang¹, Yan Xue², Laixing Zhang³

¹Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes, Institute of Plant and Food Science, School of Life Science, Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

Science (New York, N.Y.)

|October 14, 2021

まとめ

研究者らは,植物Dicer-Like Protein 3 (DCL3) 複合体の構造を明らかにし,DNAメチル化に不可欠な24核酸の小干渉RNA (siRNA) を正確に生成する方法を示した.

科学分野:

分子生物学
植物学
生物化学

背景:

小型RNA (sRNA) は,真核生物における遺伝子発現の重要な調節因子である.
ディサー内核酵素は,sRNA生殖における重要な酵素である.
植物では,DICER-LIKE PROTEIN 3 (DCL3) は,RNA誘導によるDNAメチル化に不可欠な24核性小干渉RNA (siRNAs) を生成する.

研究の目的:

活性状態のDCL3pre-siRNA複合体の構造を決定する.
DCL3の基質認識と分裂特異性の基礎にある分子メカニズムを理解する.
Dicer酵素の一般的な断片化メカニズムについての洞察を提供するためです.

主な方法:

DCL3pre-siRNA複合体の構造を決定するX線結晶学.
構造的な発見の機能的意味を検証する生化学的分析.

主要な成果:

構造は,正電荷のポケットによってガイドストランドの5'-リン酸化末端の特定の認識を明らかにします.
補足糸の1nt 3′のオーバーハングは,アロマティックキャップで認識されます.
24nt siRNAの長さの特異性は,ガイドRNAsの5'-endとリボヌクレアースIII分裂部位の間の距離によって決定される.

結論:

決定された構造は,24-nt siRNAの生成におけるDCL3の機能の詳細な分子基礎を提供する.
この発見は,DCL3の正確な認識と分裂メカニズムを明らかにします.
この研究は,種間のDicer酵素の保存された dicing原理に関する基本的な洞察を提供します.

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