title: Ribonuclease-Mediated Control of Body Fat.
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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Habacher
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland; University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Richard
authors.initials: R
authors.lastname: Venz
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Pooja
authors.initials: P
authors.lastname: Kumari
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Anca
authors.initials: A
authors.lastname: Neagu
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
authors.forename: Dimos
authors.initials: D
authors.lastname: Gaidatzis
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Villum Center for Bioanalytical Sciences, 5230 Odense M, Denmark.
authors.forename: Eva B
authors.initials: EB
authors.lastname: Harvald
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Villum Center for Bioanalytical Sciences, 5230 Odense M, Denmark.
authors.forename: Nils J
authors.initials: NJ
authors.lastname: Færgeman
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Gut
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland. Electronic address: rafal.ciosk@fmi.ch.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ciosk
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003080:Cold Temperature; D004722:Endoribonucleases / Q000378:metabolism*; D005786:Gene Expression Regulation; D049751:Genome, Helminth; D007422:Intestines / Q000201:enzymology; D008958:Models, Molecular; D034622:RNA Interference; D012260:Ribonucleases / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; C554612:ETS-4 protein, C elegans; D014157:Transcription Factors; D004722:Endoribonucleases; C000620814:REGE-1 protein, C elegans; D012260:Ribonucleases
keywords: ETS-4; MCPIP1; PIN domain; REGE-1; RNA degradation; Regnase-1; Zc3h12a; innate immunity; lipid metabolism; obesity