MicroRNA-Mediated Regulation of Dp53 in the Drosophila Fat Body Contributes to Metabolic Adaptation to Nutrient Deprivation

Epigenetic regulation in starvation is important but not fully understood yet. Here we identified the Rpd3 gene, a Drosophila homolog of histone deacetylase 1, as a critical epigenetic regulator for acquiring starvation stress resistance. Immunostaining analyses of Drosophila fat body revealed that the subcellular localization and levels of Rpd3 dynamically changed responding to starvation stress. In response to starvation stress, the level of Rpd3 rapidly increased, and it accumulated in the nucleolus in what appeared to be foci. These observations suggest that Rpd3 plays a role in regulation of rRNA synthesis in the nucleolus. The RT-qPCR and ChIP-qPCR analyses clarified that Rpd3 binds to the genomic region containing the rRNA promoters and activates rRNA synthesis in response to starvation stress. Polysome analyses revealed that the amount of polysomes was decreased in Rpd3 knockdown flies under starvation stress compared with the control flies. Since the autophagy-related proteins are known to be starvation stress tolerance proteins, we examined autophagy activity, and it was reduced in Rpd3 knockdown flies. Taken together, we conclude that Rpd3 accumulates in the nucleolus in the early stage of starvation, upregulates rRNA synthesis, maintains the polysome amount for translation, and finally increases stress tolerance proteins, such as autophagy-related proteins, to acquire starvation stress resistance.

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“…Starvation Assays were performed as described previously [39]. For starvation treatments in adults, 3 to 5 day old flies were used.…”

Section: Methodsmentioning

confidence: 99%

The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance

Nakajima¹,

Shimaji²,

Umegawachi³

et al. 2016

PLoS ONE

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“…One attractive hypothesis of coordinated, environmental-responsive gene regulation involves microRNAs (miRs). Notably, starvation reduces the levels of miR machinery components, implying the possible coupling of miR effectors to energy status (Barrio et al 2014). Several miRs have been implicated in TAG storage control, e.g., mir-278 (Teleman et al 2006) and mir-14 (Xu et al 2003;Varghese et al 2010), which both modulate energy homeostasis via insulin signaling.…”

Section: Future Perspectivesmentioning

confidence: 99%

Triacylglycerol Metabolism in Drosophila melanogaster

2018

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Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an energy source, TAG turnover is crucial to the metabolism of structural and signaling lipids. These neutral lipids are also key players in development and disease. Here, we review the metabolism of TAG in the Drosophila model system. Recently, the fruit fly has attracted renewed attention in research due to the unique experimental approaches it affords in studying the tissue-autonomous and interorgan regulation of lipid metabolism in vivo. Following an overview of the systemic control of fly body fat stores, we will cover lipid anabolic, enzymatic, and regulatory processes, which begin with the dietary lipid breakdown and de novo lipogenesis that results in lipid droplet storage. Next, we focus on lipolytic processes, which mobilize storage TAG to make it metabolically accessible as either an energy source or as a building block for biosynthesis of other lipid classes. Since the buildup and breakdown of fat involves various organs, we highlight avenues of lipid transport, which are at the heart of functional integration of organismic lipid metabolism. Finally, we draw attention to some "missing links" in basic neutral lipid metabolism and conclude with a perspective on how fly research can be exploited to study functional metabolic roles of diverse lipids.

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“…Its Drosophila orthologue, miR-305 mediates adaptive homeostasis in the intestinal stem cells of the guts (Foronda, Weng, Verma, Chen, & Cohen, 2014). It is also involved in regulation of p53 in metabolic adaptation to nutrient deprivation in the fat body (Barrio, Dekanty, & Milán, 2014). miR-34 has been used as a cellular senescence marker in human cultured cells, as the expression of this miRNA increases in senescence (Yamakuchi, Ferlito, & Lowenstein, 2008;Yamakuchi & Lowenstein, 2009).…”

Section: Introductionmentioning

confidence: 99%

Identification of miR‐305, a microRNA that promotes aging, and its target mRNAs in Drosophila

et al. 2018

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MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel Drosophila miRNAs involved in aging. We selected eight Drosophila miRNAs, displaying high homology with seed sequences of aging-related miRNAs characterized in other species, and investigated whether the over-expression of these miRNAs affected aging in Drosophila adult flies. The lifespan of adults over-expressing miR-305, a miRNA showing high homology with miR-239 in C. elegans, was significantly shorter. Conversely, a reduction in miR-305 expression led to a longer lifespan than that in control flies. miR-305 over-expression accelerated the impairment of locomotor activity and promoted the age-dependent accumulation of poly-ubiquitinated protein aggregates in the muscle, as flies aged. Thus, we show that the ectopic expression of miR-305 has a deleterious effect on aging in Drosophila. To identify the targets of miR-305, we performed RNA-Seq. We discovered several mRNAs encoding antimicrobial peptides and insulin-like peptides, whose expression changed in adults upon miR-305 over-expression. We further confirmed, by qRT-PCR, that miR-305 over-expression significantly decreases the mRNA levels of four antimicrobial peptides. As these mRNAs contain multiple sequences matching the seed sequence of miR-305, we speculate that a reduction in target mRNA levels, caused by ectopic miRNA expression, promotes aging.

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MicroRNA-Mediated Regulation of Dp53 in the Drosophila Fat Body Contributes to Metabolic Adaptation to Nutrient Deprivation

Cited by 57 publications

References 48 publications

The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance

The Histone Deacetylase Gene Rpd3 Is Required for Starvation Stress Resistance

Triacylglycerol Metabolism in Drosophila melanogaster

Identification of miR‐305, a microRNA that promotes aging, and its target mRNAs in Drosophila

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