title: Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins?
abstract: RNA silencing is a eukaryote-specific phenomenon in which microRNAs and small interfering RNAs degrade messenger RNAs containing a complementary sequence. To this end, these small RNAs need to be loaded onto an Argonaute protein (AGO protein) to form the effector complex referred to as RNA-induced silencing complex (RISC). RISC assembly undergoes multiple and sequential steps with the aid of Hsc70/Hsp90 chaperone machinery. The molecular mechanisms for this assembly process remain unclear, despite their significance for the development of gene silencing techniques and RNA interference-based therapeutics. This review dissects the currently available structures of AGO proteins and proposes models and hypotheses for RISC assembly, covering the conformation of unloaded AGO proteins, the chaperone-assisted duplex loading, and the slicer-dependent and slicer-independent duplex separation. The differences in the properties of RISC between prokaryotes and eukaryotes will also be clarified. WIREs RNA 2016, 7:637-660. doi: 10.1002/wrna.1356 For further resources related to this article, please visit the WIREs website.
authors.affiliation: Department of Chemistry & Biochemistry, The Ohio State University, Columbus, OH, USA.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D056890:Eukaryota; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D034622:RNA Interference; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex