Physiological roles for mafr-1 in reproduction and lipid homeostasis

Cell Rep. 2014 Dec 24;9(6):2180-91. doi: 10.1016/j.celrep.2014.11.035. Epub 2014 Dec 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Fertility*
  • Homeostasis
  • Intestinal Mucosa / metabolism
  • Lipid Metabolism*
  • RNA Polymerase I / genetics
  • RNA Polymerase I / metabolism
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Urogenital System / growth & development
  • Urogenital System / metabolism
  • Urogenital System / physiology
  • Vitellogenins / genetics
  • Vitellogenins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • MAFR-1 protein, C elegans
  • Repressor Proteins
  • Vitellogenins
  • Acetyltransferases
  • aminoglycoside N1-acetyltransferase
  • Fatty Acid Synthase, Type I
  • RNA Polymerase I
  • RNA Polymerase III