The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins.
Proteins of the GW182 family are essential components of the miRNA pathway in animal cells. Vertebrate genomes encode three GW182 paralogs (TNRC6A, TNRC6B, and TNRC6C), which may be functionally redundant. Here, we show that the N-terminal GW-repeat-containing regions of all three TNRC6s interact with the four human Argonaute proteins (AGO1-AGO4). We also show that TNRC6A, TNRC6B, and TNRC6C silence the expression of bound mRNAs. This activity is mediated by their C-terminal silencing domains, and thus, is independent of the interaction with AGO1-AGO4. Silencing by TNRC6A, TNRC6B, and TNRC6C is effected by changes in protein expression and mRNA stability that can, in part, be attributed to deadenylation. Our findings indicate that TNRC6A, TNRC6B, and TNRC6C are recruited to miRNA targets through an interaction between their N-terminal domain and an Argonaute protein; the TNRC6s then promote translational repression and/or degradation of miRNA targets through a C-terminal silencing domain.
Lazzaretti
Daniela
D
Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany.
Tournier
Isabelle
I
Izaurralde
Elisa
E
D000818:Animals; D060565:Argonaute Proteins; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D004331:Drosophila melanogaster / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008856:Microscopy, Fluorescence; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
C115848:AGO1 protein, human; C466422:AGO2 protein, human; C517143:AGO3 protein, human; C517144:AGO4 protein, human; D060565:Argonaute Proteins; D001324:Autoantigens; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human; C542384:TNRC6B protein, human; C540399:TNRC6C protein, human