title: The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans.
abstract: In metazoans, microRNAs (miRNAs) carry out various regulatory functions through association with multiprotein miRNA-induced silencing complexes (miRISCs) that contain Dicer and Argonaute proteins. How miRNAs regulate the expression of their mRNA targets remains a major research question. We have identified the C. elegans ain-1 gene through a genetic suppressor screen and shown that it functions with the heterochronic genetic pathway that regulates developmental timing. Biochemical analysis indicates that AIN-1 interacts with protein complexes containing an Argonaute protein, Dicer, and miRNAs. AIN-1 shares homology with the candidate human neurological disease protein GW182, shown to localize in cytoplasmic processing bodies that are sites of mRNA degradation and storage. A functional AIN-1::GFP also localizes at the likely worm processing bodies. When coexpressed from transgenes, AIN-1 targets ALG-1 to the foci. These results suggest a model where AIN-1 regulates a subset of miRISCs by localization to the processing bodies, facilitating degradation or translational inhibition of mRNA targets.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, 80309, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Morita
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D022083:Cytoplasmic Structures / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III
chemical_list: C504319:AIN-1 protein, C elegans; C558782:ALG-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D004722:Endoribonucleases; C118116:dcr-1 protein, C elegans; D043244:Ribonuclease III