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G3 (Bethesda). 2017 Aug 7;7(8):2739-2747. doi: 10.1534/g3.117.041681.

The R148.3 Gene Modulates Caenorhabditis elegans Lifespan and Fat Metabolism.

Author information

1
Quebec Heart and Lung Research Institute, G1V 4G5, Canada.
2
Faculty of Pharmacy, Laval University, Québec, G1V 0A6, Canada.
3
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada.
4
British Columbia Children's Hospital, Vancouver, V6H 3N1, Canada.
5
Department of Medical Genetics, University of British Columbia, Vancouver, V6H 3N1, Canada.
6
Centre Hospitalier de l'Université Laval (CHU) de Québec Research Center, G1V 4G2, Canada.
7
Faculty of Medicine, Laval University, Québec, G1V 0A6, Canada.
8
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4, Canada taubert@cmmt.ubc.ca Frederic.Picard@criucpq.ulaval.ca.
9
Quebec Heart and Lung Research Institute, G1V 4G5, Canada taubert@cmmt.ubc.ca Frederic.Picard@criucpq.ulaval.ca.

Abstract

Despite many advances, the molecular links between energy metabolism and longevity are not well understood. Here, we have used the nematode model Caenorhabditis elegans to study the role of the yet-uncharacterized gene R148.3 in fat accumulation and lifespan. In wild-type worms, a R148.3p::GFP reporter showed enhanced expression throughout life in the pharynx, in neurons, and in muscles. Functionally, a protein fusing a predicted 22 amino acid N-terminal signal sequence (SS) of R148.3 to mCherry displayed robust accumulation in coelomyocytes, indicating that R148.3 is a secreted protein. Systematic depletion of R148.3 by RNA interference (RNAi) at L1 but not at young-adult stage enhanced triglyceride accumulation, which was associated with increased food uptake and lower expression of genes involved in lipid oxidation. However, RNAi of R148.3 at both L1 and young-adult stages robustly diminished mean and maximal lifespan of wild-type worms, and also abolished the long-lived phenotypes of eat-2 and daf-2/InsR mutants. Based on these data, we propose that R148.3 is an SS that modulates fat mass and longevity in an independent manner.

KEYWORDS:

R148.3; daf-2; fat metabolism; insulin signaling; lifespan

PMID:
28620088
PMCID:
PMC5555478
DOI:
10.1534/g3.117.041681
[Indexed for MEDLINE]
Free PMC Article

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