[Dev Dyn.]The microRNA miR-33 is a pleiotropic regulator of metabolic and developmental processes in D. melanogaster

The microRNA miR-33 is a pleiotropic regulator of metabolic and developmental processes in D. melanogaster Dev Dyn. 2021 Apr 11. doi: 10.1002/dvdy.344. Online ahead of print. Authors Laure-Alix Clerbaux 1 2 , Hayley Schultz 3 , Samara Roman-Holba 3 , Dan Fu Ruan 3 , Ronald Yu 3 , Abigail M Lamb 4 , Guido T Bommer 1 , Jennifer A Kennell 3 Affiliations 1 Laboratory of Physiological Chemistry, de Duve Institute, Université Catholique de Louvain, Bruxelles, Belgium. 2 Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich Switzerland; Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland. 3 Department of Biology and Program in Biochemistry, Vassar College, Poughkeepsie, NY, USA. 4 Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, USA. PMID: 33840153 DOI: 10.1002/dvdy.344 Abstract Background: miR-33 family members are well characterized regulators of cellular lipid levels in mammals. Previous studies have shown that overexpression of miR-33 in Drosophila melanogaster leads to elevated triacylglycerol (TAG) levels in certain contexts. Although loss of miR-33 in flies causes subtle defects in larval and adult ovaries, the effects of miR-33 deficiency on lipid metabolism and other phenotypes impacted by metabolic state have not yet been characterized. Results: We found that loss of miR-33 predisposes flies to elevated TAG levels, and we identified genes involved in TAG synthesis as direct targets of miR-33, including atpcl, midway, and Akt1. miR-33 mutants survived longer upon starvation but showed greater sensitivity to an oxidative stressor. We also found evidence that miR-33 is a negative regulator of cuticle pigmentation and that miR-33 mutants show a reduction in interfollicular stalk cells during oogenesis. Conclusion: Our data suggest that miR-33 is a conserved regulator of lipid homeostasis, and its targets are involved in both degradation and synthesis of fatty acids and TAG. The constellation of phenotypes involving tissues that are highly sensitive to metabolic state suggests that miR-33 serves to prevent extreme fluctuations in metabolically sensitive tissues. This article is protected by copyright. All rights reserved. Keywords: lipid homeostasis; oogenesis; pigmentation; triacylglycerol.