Abstract
RNA interference (RNAi) is an essential regulatory process in embryonic development, tumor genesis and other important functions in eukaryotic cells. RNAi occurs when the Argonaute (Ago) protein brings a small non-coding RNA, such as siRNA (small interfering RNA), to target mRNA. Despite a decade of research, it remains an open question how Ago mediates specific targeting inside a crowded cell while it does not utilize any external energy such as ATP.Here we used a single-molecule FRET technique to visualize the target search process of RISC (RNA-induced silencing complex), which consists of human Ago2 and siRNA. We observed that RISC dynamically binds to and dissociates from mRNA. This dynamic interaction occurs even when there is substantial basepairing between siRNA and mRNA. RISC that dissociates from its first target is able to diffuse laterally along the RNA strand and pair with another target nearby.This dynamic search process will lead to an optimal match among many potential pairs. It hints that RISC may have evolved to compromise the search time for the target recognition fidelity. The outcome of our research will be useful in eliminating off-targeting in RNA interference.View Large Image | View Hi-Res Image | Download PowerPoint Slide
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
