miRNA广泛参与DNA损伤应答及基因组稳定性的维护，其转录、加工、运输等受到维护基因组稳定性的关键因子ATM、E2F1、p53的调节。然而，ATM/E2F1/p53如何协同调节miRNA应答DNA损伤仍缺少动物体水平的系统研究。利用果蝇模式动物和RNA-seq，本研究鉴定了应答DNA损伤或受到ATM、E2F1、p53调节的miRNA，包括44个胚胎时期及117个三期幼虫时期的miRNA；分析发现，一些miRNA受到ATM/E2F1/p53的协同调节。对部分miRNA突变果蝇DNA损伤敏感性进行检测，发现11株miRNA突变果蝇对辐照敏感，其中7株出现DNA损伤导致的凋亡增多；2株miRNA突变果蝇对辐照耐受。本研究将深入研究ATM/E2F1/p53协同调节miRNA应答DNA损伤的作用机制，从生物体水平丰富人们对机体响应DNA损伤、维护基因组稳定性的作用机制和调控网络的了解。

It is known that miRNAs are involved into DNA damage response and the maintenance of genome, and their transcription, processing, transporting are regulated by ATM, E2F1 and p53, the key factors for maintenance of genome integrity. However, systematic studies in animal levels on how ATM / E2F1 / p53 regulates miRNA in response to DNA damage coordinately is still lacking. Using the Drosophila malanogaster model animal and RNA-seq, we identified differentially expressed miRNAs after irradiation or in atm/e2f1/p53 fly mutants, which included 44 miRNAs during embryonic stage and 117 miRNAs at third instar larval stage, respectively. Furthermore, some miRNAs might be regulated coordinately by ATM/E2F1/p53. Moreover, we detected irradiation sensitivity of some established miRNA mutants, and found that 11 miRNA mutated flies were sensitive to irradiation, and in which 7 mutants showed increased apoptosis induced by DNA damage; while 2 miRNA mutants were resistant to irradiation. In this study, we will investigate the underline mechanisms of how ATM / E2F1 / p53 work coordinately to regulate miRNA in response to DNA damage, and provide further knowledge to understand genome maintenance.