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长非编码RNA CR43356-E2F1反馈调节细胞周期进程和DNA损伤应答的功能和机制研究
结题报告
批准号:
31970605
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
秘晓林
依托单位:
学科分类:
基因表达及非编码序列调控
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
秘晓林
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中文摘要
lncRNA具有广泛的生物学功能,有关它们在生物体内功能的研究还较少,并且lncRNA与关键因子E2F1如何协同调节细胞周期进程和应答DNA损伤还缺少研究。使用果蝇模式生物,本研究系统分析了e2f1突变果蝇中lncRNA的表达变化,发现lncRNA CR43356在e2f1突变果蝇中表达下调;利用已建立的lncRNA敲除果蝇进行二次筛选,发现e2f1基因在CR43356敲除果蝇中表达显著上升,并且E2F1蛋白质的表达水平也升高。RACE测序证实CR43356存在3个转录本。CR43356敲除果蝇对DNA损伤高度敏感,辐照后生存率降低,出现DNA损伤导致的凋亡细胞增多、S期检验点缺陷。本研究从生物体水平深入研究CR43356-E2F1协同调节细胞周期进程和应答DNA损伤的功能和作用机制,加深对E2F1调节机制的了解,具有重要的科学意义。
英文摘要
It is known that lncRNAs have diversified functions, however their roles in vivo are still not clear, and how E2F1, a key transcriptional factor, coordinates with lncRNAs to regulate cell cycle progression and DNA damage response is still lacking. Using Drosophila malanogaster as a model animal, we found lncRNA CR43356 was differentially expressed in e2f1 mutated flies. Using previously established CR43356 knock-out fly, we found that e2f1 expression was significantly increased in CR43356 mutant. Moreover, E2F1 protein level was also greatly increased in CR43356 mutant. We identified 3 transcripts of CR43356 using the RACE-seq method. Furthermore, the CR43356 knock-out flies were hypersensitive to irradiation, showing greatly reduced viability, increased apoptosis, and S phase checkpoint defect. In this study, we will investigate the underlying mechanisms of how lncRNA CR43356-E2F1 work coordinately to regulate cell cycle progression and DNA damage response, to improve our understanding towards regulation of E2F1, and provide novel knowledge to understand cell cycle regulation and genome maintenance.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Distinct and Coordinated Regulation of Small Non-coding RNAs by E2f1 and p53 During Drosophila Development and in Response to DNA Damage.
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
发表时间:2021
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Li D;Ge Y;Zhao Z;Zhu R;Wang X;Bi X
通讯作者:Bi X
DOI:10.1093/genetics/iyad040
发表时间:2023
期刊:Genetics
影响因子:--
作者:Qi Xu;Jun Liu;Xiao Du;Di Xue;Dong Li;Xiaolin Bi
通讯作者:Xiaolin Bi
长非编码RNA CR45811调节宿主基因trio的表达和组织稳态的功能和机制研究
  • 批准号:
    --
  • 项目类别:
    面上项目
  • 资助金额:
    54万元
  • 批准年份:
    2022
  • 负责人:
    秘晓林
  • 依托单位:
国内基金
海外基金