MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies.
Small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs) can silence target genes through several different effector mechanisms. Whereas siRNA-directed mRNA cleavage is increasingly understood, the mechanisms by which miRNAs repress protein synthesis are obscure. Recent studies have revealed the existence of specific cytoplasmic foci, referred to herein as processing bodies (P-bodies), which contain untranslated mRNAs and can serve as sites of mRNA degradation. Here we demonstrate that Argonaute proteins--the signature components of the RNA interference (RNAi) effector complex, RISC--localize to mammalian P-bodies. Moreover, reporter mRNAs that are targeted for translational repression by endogenous or exogenous miRNAs become concentrated in P-bodies in a miRNA-dependent manner. These results provide a link between miRNA function and mammalian P-bodies and suggest that translation repression by RISC delivers mRNAs to P-bodies, either as a cause or as a consequence of inhibiting protein synthesis.
Liu
Jidong
J
Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Valencia-Sanchez
Marco Antonio
MA
Hannon
Gregory J
GJ
Parker
Roy
R
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D022083:Cytoplasmic Structures / Q000378:metabolism*; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000502:physiology; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism; D014162:Transfection
D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins; D015852:Eukaryotic Initiation Factor-2; D035683:MicroRNAs; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D034743:RNA-Induced Silencing Complex; D019718:Receptors, CXCR4; D015534:Trans-Activators; C474488:let-7 microRNA, C elegans; D004722:Endoribonucleases; C466279:DCP1A protein, human; C467723:DCP2 protein, human