title: The let-7 microRNA directs vulval development through a single target.
abstract: The let-7 microRNA (miRNA) regulates stemness in animals ranging from worms to humans. However, the cause of the dramatic vulval rupturing phenotype of let-7 mutant C. elegans has remained unknown. Consistent with the notion that miRNAs function by coordinately tuning the expression of many targets, bursting may result from joint dysregulation of several targets, possibly in the epidermis. Alternatively, overexpression of LET-60/RAS, a key vulva development gene and a phylogenetically conserved target of let-7, may be responsible. Here, we show that let-7 functions in the vulval-uterine system to ensure vulval integrity but that regulation of most targets of let-7, including LET-60/RAS, is dispensable. Using CRISPR-Cas9 to edit endogenous let-7 target sites, we found that regulation of LIN-41/TRIM71 alone is necessary and sufficient to prevent vulval rupturing. Hence, let-7 does not function to reduce gene expression noise broadly, but to direct vulval development through extensive regulation of a single, defined target.
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors: Matyas
authors: M
authors: Ecsedi
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors: Magdalene
authors: M
authors: Rausch
authors: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: helge.grosshans@fmi.ch.
authors: Helge
authors: H
authors: Großhans
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D038081:Organogenesis / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014844:Vulva / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C410586:LIN-41 protein, C elegans; D035683:MicroRNAs; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans; D018631:ras Proteins