Human Argonaute 2 has diverse reaction pathways on target RNAs

\"Human Argonaute 2 has diverse reaction pathways on target RNAs\", Molecular Cell
Authors: Myung Hyun Jo*, Soochul Shin*, Seung-Ryoung Jung, Eunji Kim, Ji-Joon Song, and Sungchul Hohng
*equal contribution

Argonaute은 진핵생명의 유전자 발현을 조절하는 RNAi현상을 실제로 발현하는 단백질로 miRNA 등과 결합하여 RISC라는 RNA-단백질 복합체를 형성한다. 홍성철 교수님 연구팀은 단일분자 수준의 연구를 통해, RISC가 target RNA를 찾아 target에 결합한 뒤 단순 해리, 절단, guide RNA unloading, stable binding의 다양한 반응 경로를 가질 수 있다는 것을 밝혀내었다.

Summary
Argonaute is a key enzyme of various RNA silencing pathways. We use single-molecule fluorescence measurements to characterize the reaction mechanisms of the core-RISC (RNA-induced silencing complex) composed of human Argonaute 2 and a small RNA. We found that target binding of core-RISC starts at the seed region, resulting in four distinct reaction pathways: target cleavage, transient binding, stable binding, and Argonaute unloading. The target cleavage requires extensive sequence complementarity and dramatically accelerates core-RISC recycling. The stable binding of core-RISC is efficiently established with the seed match only, providing a potential explanation for the seed-match rule of miRNA (microRNA) target selection. Target cleavage on perfect-match targets sensitively depends on RNA sequences, providing an insight into designing more efficient siRNAs (small interfering RNAs).