Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies.
RNA interference (RNAi) is an important means of eliminating mRNAs, but the intracellular location of RNA-induced silencing complex (RISC) remains unknown. We show here that Argonaute 2, a key component of RISC, is not randomly distributed but concentrates in mRNA decay centres that are known as cytoplasmic bodies. The localization of Argonaute 2 in decay centres is not altered by the presence or absence of small interfering RNAs or their targeted mRNAs. However, RNA is required for the integrity of cytoplasmic bodies because RNase eliminates Argonaute 2 localization. In addition, Argonaute 1, another Argonaute family member, is concentrated in cytoplasmic bodies. These results provide new insight into the mechanism of RNAi function.
Sen
George L
GL
Department of Molecular Pharmacology, 269 Campus Drive, CCSR 4225A, Stanford University School of Medicine, Stanford, CA 94305, USA.
Blau
Helen M
HM
D000818:Animals; D060565:Argonaute Proteins; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D051379:Mice; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*; D000099254:Organic Cation Transporter 3
D060565:Argonaute Proteins; D001324:Autoantigens; D015852:Eukaryotic Initiation Factor-2; D046911:Macromolecular Substances; D027701:Organic Cation Transport Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D000099254:Organic Cation Transporter 3; C466422:AGO2 protein, human; C465663:TNRC6A protein, human