Distinct and Coordinated Regulation of Small Non-coding RNAs by E2f1 and p53 During Drosophila Development and in Response to DNA Damage.

Distinct and Coordinated Regulation of Small Non-coding RNAs by E2f1 and p53 During Drosophila Development and in Response to DNA Damage.
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果蝇发育过程中 E2f1 和 p53 对小非编码 RNA 的独特和协调调节以及对 DNA 损伤的反应。

DOI:
10.3389/fcell.2021.695311
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发表时间:
2021
影响因子:
5.5
通讯作者:
Bi X
Bi X
中科院分区:
生物学2区
文献类型:
--
作者:
Li D;Ge Y;Zhao Z;Zhu R;Wang X;Bi X

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小的非编码RNA(ncRNA),包括microRNA(miRNAs)和PIWI相互作用RNA(piRNA),在生物过程中起着关键作用。在发育过程中和DNA损伤反应(DDR)中小ncRNA表达的全面定量参考将显着促进我们对其作用的理解。本研究系统分析了野生型果蝇、e2f1突变型果蝇、p53突变型果蝇和e2f1 p53双突变型果蝇在发育过程中和X射线照射后的miRNAs和piRNAs表达谱。通过小RNA测序和生物信息学分析,我们发现miRNAs和piRNAs都以动态模式表达,并在发育过程中形成4个不同的簇。值得注意的是,miRNAs和piRNAs的表达模式在e2f1突变体中在多个发育阶段发生变化,而在p53突变体中保持不变,表明E2f1在介导小ncRNAs表达中起关键作用。此外,我们确定了差异表达(DE)的小ncRNAs在e2f1突变体和p53突变体后,X射线照射。此外,我们绘制了E2f1和p53在小ncRNA周围的结合基序。我们的数据表明,E2f1和p53的工作方式不同,但协调调节小ncRNAs的表达,E2f1可能发挥主要作用,在发育过程中和X射线照射后调节miRNA。总的来说,我们的研究结果提供了小ncRNA的全面表征,以及E2f1和p53在小ncRNA表达,发育过程中和DNA损伤反应中的调节作用,这揭示了对小ncRNA生物学的新见解。
Small non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), play a pivotal role in biological processes. A comprehensive quantitative reference of small ncRNAs expression during development and in DNA damage response (DDR) would significantly advance our understanding of their roles. In this study, we systemically analyzed the expression profile of miRNAs and piRNAs in wild-type flies, e2f1 mutant, p53 mutant and e2f1 p53 double mutant during development and after X-ray irradiation. By using small RNA sequencing and bioinformatic analysis, we found that both miRNAs and piRNAs were expressed in a dynamic mode and formed 4 distinct clusters during development. Notably, the expression pattern of miRNAs and piRNAs was changed in e2f1 mutant at multiple developmental stages, while retained in p53 mutant, indicating a critical role of E2f1 played in mediating small ncRNAs expression. Moreover, we identified differentially expressed (DE) small ncRNAs in e2f1 mutant and p53 mutant after X-ray irradiation. Furthermore, we mapped the binding motif of E2f1 and p53 around the small ncRNAs. Our data suggested that E2f1 and p53 work differently yet coordinately to regulate small ncRNAs expression, and E2f1 may play a major role to regulate miRNAs during development and after X-ray irradiation. Collectively, our results provide comprehensive characterization of small ncRNAs, as well as the regulatory roles of E2f1 and p53 in small ncRNAs expression, during development and in DNA damage response, which reveal new insights into the small ncRNAs biology.
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