Abstract
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).
Original language | English (US) |
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Pages (from-to) | 117-124 |
Number of pages | 8 |
Journal | Molecular cell |
Volume | 59 |
Issue number | 1 |
DOIs | |
State | Published - 2015 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology