鉴定因应DNA损伤而诱导的ATM依赖的长非编码RNA
Marta Podralska1, Marcin Piotr Sajek2, Antonina Bielicka1
1Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
DNA repair
|February 21, 2024
概括
这项研究以ATM依赖的方式识别了由DNA损伤诱导的长非编码RNA (lncRNAs). 这些ncRNAs可能在调节参与DNA损伤反应的基因中发挥作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- DNA双链断裂 (DSB) 是关键的DNA损伤事件.
- ATM 激酶是DNA损伤反应 (DDR) 的核心.
- 长非编码RNAs (lncRNAs) 越来越多地被认为是它们在细胞过程中的角色.
研究的目的:
- 以ATM-依赖的方式识别因DNA损伤引起的lncRNAs.
- 研究 lncRNAs 在细胞对DNA损伤反应中的作用.
主要方法:
- 电离辐射 (IR) 用于诱导DNA损伤从健康的捐赠者和 - 脑膜异位症 (AT) 患者的淋巴细胞细胞系.
- 进行RNA测序 (RNA-seq) 来分析lncRNA和mRNA的表达.
- 定量实时PCR (RT-qPCR) 验证了 lncRNA的诱导.
- 用ATM抑制和亚细胞分离来进一步描述lncRNA的功能和局部化.
主要成果:
- 10和149个lncRNA分别在1h和8h时在健康捐赠者中被IR显著诱导,AT患者的诱导最小.
- 对于诱导这些IR响应的lncRNAs来说,ATM激酶活性至关重要.
- 基因表达分析显示,AT患者的DDR通路激活延迟.
- 许多已识别的lncRNA位于DDR相关基因附近,它们的诱导在相邻基因表达的变化之前发生.
- 大多数研究的lncRNA被发现是染色体局部化的.
结论:
- 几种lncRNAs是由电离辐射以ATM依赖的方式诱导的.
- 这些lncRNAs可能作为参与DNA损伤反应的附近基因的调节者.
- 这些发现突出了lncRNAs在复杂的DNA损伤反应网络中的新角色.
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