AsianScientist (Jul. 10, 2015) – Researchers have revealed the molecular mechanism of RNA interference (RNAi) by real time observation of target RNA cleavage at the single-molecule level. Their results have been published in Molecular Cell and featured on the cover of the journal.
RNAi, which is used by cells to inhibit the translation of specific proteins, has become a valuable research tool. In the future, the phenomenon of RNAi is expected to find applications in medical treatments.
RNAi is mediated by the RNA-induced silencing complex (RISC), which contains a small RNA molecule and an Argonaute protein at its core that cleaves the target RNA. However, there were no suitable tools to directly monitor the RNAi reaction and its molecular mechanism by which RISC cleaves the target RNA has remained unclear.
In the present study, researchers at the University of Tokyo and Kyoto University led by Professor Hisashi Tadakuma have developed a single-molecule imaging assay for observing target RNA cleavage by RISC in a test tube in real time, showing how RISC accurately cleaves and releases targets.
Specifically, their observations provide direct evidence for the model that the small RNA in the RISC consists of two parts, one of which quickly binds to the target RNA to be cleaved, while the other proofreads that the correct RNA has been found.
This result reveals RISC’s molecular mechanism of action. The authors anticipate their their findings will contribute to accelerating the research applications of RNAi such as to the development of RNA-based next-generation drugs, for example as gene therapy to suppress the production of a disease-causing protein.
The article can be found at: Yao et al. (2015) Single-Molecule Analysis of the Target Cleavage Reaction by the Drosophila RNAi Enzyme Complex.
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Source: University of Tokyo.
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