Evolutionary conservation analysis reveals a primordial function of STING as a regulator of lipid metabolism via FADS2
Abstract
The stimulator of interferon genes (STING) is a pivotal regulator of type I interferon (IFN) responses. Although the IFN system is confined to vertebrates, STING is present across metazoans and in some unicellular eukaryotes, suggesting involvement in distinct functions prior to vertebrate divergence. Here we explore the conservation of STING-mediated regulation of polyunsaturated fatty acid (PUFA) metabolism. We find that STING homologs from vertebrates, invertebrates, and unicellular eukaryotes interact with fatty acid desaturase 2 (FADS2), the rate-limiting enzyme in PUFA metabolism, and influence subsequent functional outputs. Specifically, we show that STING homologs differentially shape cell susceptibility to infection by DNA and RNA viruses independently of the activation of IFN responses, suggesting that STING-mediated metabolic pathway regulation may participate in primitive host defense mechanisms. Thus, we identify STING-mediated metabolic regulation as an evolutionarily conserved feature and a primordial function of STING.
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BibTeX
@article{guha2026evolutionary,
title = {{Evolutionary conservation analysis reveals a primordial function of STING as a regulator of lipid metabolism via FADS2}},
author = {Soumyabrata Guha and Joanna Re and Stéphane Grégoire and Morgane Chemarin and Adeline Augereau and Yasmine Messaoud-Nacer and Pierre Le Hars and Hanane Chamma and Victoria Bergas and Collin Mcnairy and Jenny Nguyen and Jennifer Barrat and Jean-Paul Pais de Barros and Arielle Woznica and Niyazi Acar and Isabelle Vila and Pierre Boudinot and Nadine Laguette},
journal = {Nature Communications},
year = {2026},
month = aug,
doi = {10.1038/s41467-026-76833-5},
url = {https://hal.science/hal-05760249v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evolutionary conservation analysis reveals a primordial function of STING as a regulator of lipid metabolism via FADS2
AU - Soumyabrata Guha
AU - Joanna Re
AU - Stéphane Grégoire
AU - Morgane Chemarin
AU - Adeline Augereau
AU - Yasmine Messaoud-Nacer
AU - Pierre Le Hars
AU - Hanane Chamma
AU - Victoria Bergas
AU - Collin Mcnairy
AU - Jenny Nguyen
AU - Jennifer Barrat
AU - Jean-Paul Pais de Barros
AU - Arielle Woznica
AU - Niyazi Acar
AU - Isabelle Vila
AU - Pierre Boudinot
AU - Nadine Laguette
PY - 2026
DA - 2026/08/14
JO - Nature Communications
DO - 10.1038/s41467-026-76833-5
UR - https://hal.science/hal-05760249v1
AB - The stimulator of interferon genes (STING) is a pivotal regulator of type I interferon (IFN) responses. Although the IFN system is confined to vertebrates, STING is present across metazoans and in some unicellular eukaryotes, suggesting involvement in distinct functions prior to vertebrate divergence. Here we explore the conservation of STING-mediated regulation of polyunsaturated fatty acid (PUFA) metabolism. We find that STING homologs from vertebrates, invertebrates, and unicellular eukaryotes interact with fatty acid desaturase 2 (FADS2), the rate-limiting enzyme in PUFA metabolism, and influence subsequent functional outputs. Specifically, we show that STING homologs differentially shape cell susceptibility to infection by DNA and RNA viruses independently of the activation of IFN responses, suggesting that STING-mediated metabolic pathway regulation may participate in primitive host defense mechanisms. Thus, we identify STING-mediated metabolic regulation as an evolutionarily conserved feature and a primordial function of STING.
SN - 2041-1723
SN - 2041-1723
ER -