The microRNA miR‐33 is a pleiotropic regulator of metabolic and developmental processes in Drosophila melanogaster

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.

Non-coding RNAs identification and regulatory networks in pathogen-host interaction in the microsporidia congenital infection

“…For B. mori miRNAs, we found that there was significantly decreased in the number of miRNAs in the silkworm embryos and larvae exposed to the congenital N. bombycis challenge, compared with uninfected embryos and larvae. Both miRNA-33 and miRNA-122, which can target lipid metabolism genes to reprogram host lipid metabolism [68][69][70], are down-regulated during the congenital N. bombycis infection. miR-276 is associated with amino acid metabolism [71], which is down-regulated during the congenital N. bombycis infection.…”

Non-coding RNAs identification and regulatory networks in pathogen-host interaction in the microsporidia congenital infection

“…For B. mori miRNAs, we found that there was signi cantly decreased in the number of miRNAs in the silkworm embryos and larvae exposed to the congenital N. bombycis challenge, compared with uninfected embryos and larvae. Both miRNA-33 and miRNA-122, which can target lipid metabolism genes to reprogram host lipid metabolism [53][54][55], are down-regulated during the congenital N. bombycis infection. miR-276 is associated with amino acid metabolism [56], which is downregulated during the congenital N. bombycis infection.…”

Inhibition of Drosophila microRNA-6 increases lipid droplet accumulation in cardiomyocytes but mitigates age-related cardiac arrhythmia and extends lifespan

“…The conserved microRNA, miR-1, for example, has been shown to regulate a number of targets that impact heart structure and function in Drosophila, with implications for human health [38][39]. The conserved microRNA, miR-33, on the other hand, has been established as a key regulator of glucose and lipid metabolism [40][41]. In addition, several microRNAs, such as miR-34 and let-7, are conserved between Drosophila and humans and have been connected to longevity through a variety of mechanisms including, neuronal dysregulation, insulin/TOR signaling, and mitochondria maintenance/ROS production [42].…”