Ribonuclease-Mediated Control of Body Fat

Dev Cell. 2016 Nov 7;39(3):359-369. doi: 10.1016/j.devcel.2016.09.018. Epub 2016 Oct 13.


Obesity is a global health issue, arousing interest in molecular mechanisms controlling fat. Transcriptional regulation of fat has received much attention, and key transcription factors involved in lipid metabolism, such as SBP-1/SREBP, LPD-2/C/EBP, and MDT-15, are conserved from nematodes to mammals. However, there is a growing awareness that lipid metabolism can also be controlled by post-transcriptional mechanisms. Here, we show that the Caenorhabditis elegans RNase, REGE-1, related to MCPIP1/Zc3h12a/Regnase-1, a key regulator of mammalian innate immunity, promotes accumulation of body fat. Using exon-intron split analysis, we find that REGE-1 promotes fat by degrading the mRNA encoding ETS-4, a fat-loss-promoting transcription factor. Because ETS-4, in turn, induces rege-1 transcription, REGE-1 and ETS-4 appear to form an auto-regulatory module. We propose that this type of fat regulation may be of key importance when, if faced with an environmental change, an animal must rapidly but precisely remodel its metabolism.

Keywords: ETS-4; MCPIP1; PIN domain; REGE-1; RNA degradation; Regnase-1; Zc3h12a; innate immunity; lipid metabolism; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adipose Tissue / metabolism*
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cold Temperature
  • Endoribonucleases / metabolism*
  • Gene Expression Regulation
  • Genome, Helminth
  • Intestines / enzymology
  • Models, Molecular
  • RNA Interference
  • Ribonucleases / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • ETS-4 protein, C elegans
  • Transcription Factors
  • Endoribonucleases
  • REGE-1 protein, C elegans
  • Ribonucleases