Structural insights into the human GW182-PABC interaction in microRNA-mediated deadenylation.
GW182-family proteins are essential for microRNA-mediated translational repression and deadenylation in animal cells. Here we show that a conserved motif in the human GW182 paralog TNRC6C interacts with the C-terminal domain of polyadenylate binding protein 1 (PABC) and present the crystal structure of the complex. Mutations at the complex interface impair mRNA deadenylation in mammalian cell extracts, suggesting that the GW182-PABC interaction contributes to microRNA-mediated gene silencing.
Jinek
Martin
M
Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
Fabian
Marc R
MR
Coyle
Scott M
SM
Sonenberg
Nahum
N
Doudna
Jennifer A
JA
D019943:Amino Acid Substitution / Q000235:genetics; D018360:Crystallography, X-Ray; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D039122:Poly(A)-Binding Protein I / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020836:Protein Structure, Quaternary; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*
D035683:MicroRNAs; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C540399:TNRC6C protein, human