Format

Send to

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

Ribonuclease-Mediated Control of Body Fat.

Author information

1
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
2
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
3
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
4
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Villum Center for Bioanalytical Sciences, 5230 Odense M, Denmark.
5
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. Electronic address: rafal.ciosk@fmi.ch.

Abstract

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

PMID:
27746047
DOI:
10.1016/j.devcel.2016.09.018
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center