Abstract:
:Argonaute (Ago) proteins are the key component of the RNA-induced silencing complex and mediate RNA interference (RNAi) in association with small RNAs. Although overall the mechanism of RNAi is well understood, many molecular details of this complex process are not. Here we report about in-depth steady-state and, in particular, pre-steady-state characterization of siRNA binding, target RNA recognition, sequence-specific cleavage and product release by recombinant human Ago 2 (hAgo2). In combining our biochemical studies with crystal structures of bacterial Ago proteins and of recently released hAgo2, we relate kinetic data to conformational changes along the pathway and propose a comprehensive minimal mechanistic model describing fundamental steps during RNAi. Furthermore, in contrast to the current conception, our hAgo2 preparations are programmable with double-stranded siRNA. Accordingly, the system investigated represents a functional minimal RNA-induced silencing complex.
journal_name
Proc Natl Acad Sci U S Aauthors
Deerberg A,Willkomm S,Restle Tdoi
10.1073/pnas.1217838110subject
Has Abstractpub_date
2013-10-29 00:00:00pages
17850-5issue
44eissn
0027-8424issn
1091-6490pii
1217838110journal_volume
110pub_type
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