转录因子Myc是一种保守的调节细胞生长、增殖和凋亡的因子，其失调与人类病理有关。尽管特定的miRNA已被确定为Myc致瘤程序的基本组成部分，但Myc如何调控miRNA生成仍然存在争议。在这里，我们展示了Myc在果蝇中作为miRNA生成的重要调控因子，通过影响miRNA基因表达和处理。通过对ChIP-Seq序列数据的分析，我们发现近56%的果蝇miRNA基因表现出dMyc结合，其峰值区域内存在规范或非规范E-box序列。一致地，dMyc水平的降低导致miRNA基因表达的广泛下调。dMyc还通过直接转录调控控制Drosha和AGO1水平，调节miRNA处理和活性。通过使用体内miRNA活性传感器，我们证明了dMyc在不同组织中促进了miRNA介导的沉默作用，包括翅膀起源和脂肪体。我们还显示了脂肪体中dMyc依赖的miR-305表达根据营养可利用性调节Dmp53水平，在有机体对营养压力的响应能力上产生了重大影响。实际上，脂肪体中的dMyc消耗导致对营养匮乏的延长存活，这可以通过miR-305或Dmp53的负性显性表达逆转。我们的研究揭示了一个以前未被认识到的dMyc作为miRNA生成的重要调控因子的功能，并暗示Myc依赖的特定miRNA的表达可能具有重要的组织特异性功能。 版权：© 2023 Gervé等人。本文采用创作共用授权许可证发表，允许在任何媒介中无限制使用、分发和复制，只要原始作者和出处被署名。

The conserved transcription factor Myc regulates cell growth, proliferation and apoptosis, and its deregulation has been associated with human pathologies. Although specific miRNAs have been identified as fundamental components of the Myc tumorigenic program, how Myc regulates miRNA biogenesis remains controversial. Here we showed that Myc functions as an important regulator of miRNA biogenesis in Drosophila by influencing both miRNA gene expression and processing. Through the analysis of ChIP-Seq datasets, we discovered that nearly 56% of Drosophila miRNA genes show dMyc binding, exhibiting either the canonical or non-canonical E-box sequences within the peak region. Consistently, reduction of dMyc levels resulted in widespread downregulation of miRNAs gene expression. dMyc also modulates miRNA processing and activity by controlling Drosha and AGO1 levels through direct transcriptional regulation. By using in vivo miRNA activity sensors we demonstrated that dMyc promotes miRNA-mediated silencing in different tissues, including the wing primordium and the fat body. We also showed that dMyc-dependent expression of miR-305 in the fat body modulates Dmp53 levels depending on nutrient availability, having a profound impact on the ability of the organism to respond to nutrient stress. Indeed, dMyc depletion in the fat body resulted in extended survival to nutrient deprivation which was reverted by expression of either miR-305 or a dominant negative version of Dmp53. Our study reveals a previously unrecognized function of dMyc as an important regulator of miRNA biogenesis and suggests that Myc-dependent expression of specific miRNAs may have important tissue-specific functions.Copyright: © 2023 Gervé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.