title: The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25.
abstract: The let-7 microRNA (miRNA) gene of Caenorhabditis elegans controls the timing of developmental events. let-7 is conserved throughout bilaterian phylogeny and has multiple paralogs. Here, we show that the paralog mir-84 acts synergistically with let-7 to promote terminal differentiation of the hypodermis and the cessation of molting in C. elegans. Loss of mir-84 exacerbates phenotypes caused by mutations in let-7, whereas increased expression of mir-84 suppresses a let-7 null allele. Adults with reduced levels of mir-84 and let-7 express genes characteristic of larval molting as they initiate a supernumerary molt. mir-84 and let-7 promote exit from the molting cycle by regulating targets in the heterochronic pathway and also nhr-23 and nhr-25, genes encoding conserved nuclear hormone receptors essential for larval molting. The synergistic action of miRNA paralogs in development may be a general feature of the diversified miRNA gene family.
authors.affiliation: Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Hayes
authors.forename: Alison R
authors.initials: AR
authors.lastname: Frand
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D018978:Molting / Q000235:genetics / Q000502:physiology; D009154:Mutation; D018510:RNA, Helminth / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D018510:RNA, Helminth; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans; C486359:nuclear hormone receptor NHR-25, C elegans