A microRNA in a multiple-turnover RNAi enzyme complex.
In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. Here we show that, in human cell extracts, the miRNA let-7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function. Human let-7 is a component of a previously identified, miRNA-containing ribonucleoprotein particle, which we show is an RNAi enzyme complex. Each let-7-containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells.
Hutvágner
György
G
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA.
Zamore
Phillip D
PD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D060565:Argonaute Proteins; D020029:Base Pairing; D001483:Base Sequence; D002457:Cell Extracts; D003593:Cytoplasm / Q000378:metabolism; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D004331:Drosophila melanogaster / Q000235:genetics; D004722:Endoribonucleases / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D020365:RNA Helicases / Q000378:metabolism; D016372:RNA, Antisense / Q000737:chemistry / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000737:chemistry / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex; D043244:Ribonuclease III; D012261:Ribonucleoproteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear
C115848:AGO1 protein, human; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D002457:Cell Extracts; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; C406815:GEMIN4 protein, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D010448:Peptide Initiation Factors; D016372:RNA, Antisense; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D034743:RNA-Induced Silencing Complex; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D000255:Adenosine Triphosphate; D004722:Endoribonucleases; D043244:Ribonuclease III; C120168:DDX20 protein, human; D055541:DEAD Box Protein 20; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases