一种新的AluYb8插入关联的非编码RNA,IncMUTYH,损害了线粒体功能,并抑制了巨细胞的M2样两极分化
Gaochao Dong1,2,3, Xuewen Yin2,3,4, Yingkuan Liang2,3
1Department of Medical Genetics, Medical School, Nanjing University, Nanjing, China.
Free radical research
|December 25, 2023
概括
一种来自AluYb8插入的新型长非编码RNA,IncMUTYH,抑制MUTYH1的表达,导致线粒体功能障碍和巨细胞极化受损,可能导致与年龄相关的疾病.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 在MUTYH内15 (AluYb8MUTYH变体) 中插入AluYb8与减少MUTYH1表达和与年龄相关的线粒体功能障碍有关.
- 这种关联背后的精确分子机制仍然不清楚.
研究的目的:
- 阐明AluYb8MUTYH变体影响MUTYH1表达和线粒体功能的机制.
- 为了识别和描述与AluYb8MUTYH变异相关的新型转录.
主要方法:
- 一个新的非编码转录的识别和特征, lncMUTYH.
- 报告者基因测试以评估IncMUTYH对MUTYH1表达的调节作用.
- 针对位点的突变发生,以调查lncMUTYH和MUTYH1.1.之间的相互作用.
- 分析线粒体功能指标 (mtDNA含量,基因表达,氧气消耗,ATP生产,呼吸能力).
- 对巨细胞极化 (M2类) 和细胞表面标记物的评估 (CD68,CD206).
主要成果:
- 一个新的转录,IncMUTYH,被确定,缺乏蛋白质编码潜力.
- 证实lncMUTYH通过与MUTYH1 5'UTR的部分基配对在翻译层面下调MUTYH1的表达.
- lncMUTYH的表达与线粒体功能下降和M2型巨细胞两极分化受损相关.
- lncMUTYH作为一种转调节因子,抑制MUTYH1蛋白表达.
结论:
- 与 AluYb8MUTYH 相关的 lncMUTYH 抑制了 MUTYH1 的表达,导致线粒体功能障碍.
- lncMUTYH破坏了巨细胞的两极分化,可能增加与年龄有关的疾病的风险.
- lncMUTYH是AluYb8MUTYH相关的线粒体功能障碍和与年龄相关的疾病的关键调解者.
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