title: Physiological roles for mafr-1 in reproduction and lipid homeostasis.
abstract: Maf1 is a conserved repressor of RNA polymerase (Pol) III transcription; however, its physiological role in the context of a multicellular organism is not well understood. Here, we show that C. elegans MAFR-1 is functionally orthologous to human Maf1, represses the expression of both RNA Pol III and Pol II transcripts, and mediates organismal fecundity and lipid homeostasis. MAFR-1 impacts lipid transport by modulating intestinal expression of the vitellogenin family of proteins, resulting in cell-nonautonomous defects in the developing reproductive system. MAFR-1 levels inversely correlate with stored intestinal lipids, in part by influencing the expression of the lipogenesis enzymes fasn-1/FASN and pod-2/ACC1. Animals fed a high carbohydrate diet exhibit reduced mafr-1 expression and mutations in the insulin signaling pathway genes daf-18/PTEN and daf-16/FoxO abrogate the lipid storage defects associated with deregulated mafr-1 expression. Our results reveal physiological roles for mafr-1 in regulating organismal lipid homeostasis, which ensure reproductive success.
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA; Department of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Akshat
authors.initials: A
authors.lastname: Khanna
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Johnson
authors.affiliation: Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA; Department of Molecular and Computational Biology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USA; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: spcurran@usc.edu.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Curran
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005298:Fertility; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000378:metabolism; D050356:Lipid Metabolism; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014566:Urogenital System / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C000599610:MAFR-1 protein, C elegans; D012097:Repressor Proteins; D014819:Vitellogenins; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D054890:Fatty Acid Synthase, Type I; D012318:RNA Polymerase I; D012320:RNA Polymerase III