title: The Caenorhabditis elegans GW182 protein AIN-1 interacts with PAB-1 and subunits of the PAN2-PAN3 and CCR4-NOT deadenylase complexes.
abstract: GW182 family proteins are essential for miRNA-mediated gene silencing in animal cells. They are recruited to miRNA targets via interactions with Argonaute proteins and then promote translational repression and degradation of the miRNA targets. The human and Drosophila melanogaster GW182 proteins share a similar domain organization and interact with PABPC1 as well as with subunits of the PAN2-PAN3 and CCR4-NOT deadenylase complexes. The homologous proteins in Caenorhabditis elegans, AIN-1 and AIN-2, lack most of the domains present in the vertebrate and insect proteins, raising the question as to how AIN-1 and AIN-2 contribute to silencing. Here, we show that both AIN-1 and AIN-2 interact with Argonaute proteins through GW repeats in the middle region of the AIN proteins. However, only AIN-1 interacts with C. elegans and D. melanogaster PABPC1, PAN3, NOT1 and NOT2, suggesting that AIN-1 and AIN-2 are functionally distinct. Our findings reveal a surprising evolutionary plasticity of the GW182 protein interaction network and demonstrate that binding to PABPC1 and deadenylase complexes has been maintained throughout evolution, highlighting the significance of these interactions for silencing.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.
authors.forename: Duygu
authors.initials: D
authors.lastname: Kuzuoglu-Öztürk
authors.forename: Eric
authors.initials: E
authors.lastname: Huntzinger
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmidt
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000037:antagonists & inhibitors; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors; D020868:Gene Silencing; D039122:Poly(A)-Binding Protein I / Q000737:chemistry / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012260:Ribonucleases / Q000378:metabolism*
chemical_list: C504319:AIN-1 protein, C elegans; C525939:AIN-2 protein, C elegans; C558782:ALG-1 protein, C elegans; D060565:Argonaute Proteins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; C513405:Gw protein, Drosophila; D039122:Poly(A)-Binding Protein I; D021122:Protein Subunits; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012260:Ribonucleases; C445084:mRNA deadenylase