title: A microRNA family exerts maternal control on sex determination inC. elegans.
abstract: Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally contributed microRNAs may therefore play important roles in early development. We elucidated a major biological role of the nematodemir-35family of maternally contributed essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream of and downstream fromher-1to prevent aberrantly activated male developmental programs in hermaphrodite embryos. Both of the predicted target genes that act downstream from themir-35family in this process,suppressor-26(sup-26) andNHL(NCL-1, HT2A, and LIN-41 repeat) domain-containing-2 (nhl-2), encode RNA-binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway ofCaenorhabditis elegansRepression ofnhl-2by themir-35family is required for not only proper sex determination but also viability, showing that a single microRNA target site can be essential. Since sex determination inC. elegansrequires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-naïve; our findings show that themir-35family microRNAs act in the early embryo to function as a developmental timer that preserves naïveté and prevents premature deleterious developmental decisions.
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: McJunkin
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D016601:RNA-Binding Proteins / Q000378:metabolism; D019849:Sex Determination Processes / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; C570417:MIRN35 microRNA, C elegans; D035683:MicroRNAs; D016601:RNA-Binding Proteins
keywords: embryonic development; maternal control; microRNAs; mir-35–41; mir-35–42; sex determination