在WTAP中介的N6-甲基氨酸RNA修改ELF3驱动细胞衰老通过UpregulatingIRF8
Lei Zhou1,2, Yun Zhong3,1, Fan Wang3,1
1Hunan key laboratory of aging biology, Xiangya Hospital, Central South University, Changsha, P.R. China.
International journal of biological sciences
|March 14, 2024
概括
威尔姆斯威尔姆斯是什么意思
科学领域:
- 分子生物学分子生物学
- 皮肤病学 皮肤病学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- N6-甲基氨酸 (m6A) 是一种关键的RNA修饰,影响细胞功能和疾病.
- m6A在皮肤衰老机制中的作用在很大程度上仍未被探索.
- 细胞衰老是衰老的标志,但其通过皮肤m6A的调节尚不清楚.
研究的目的:
- 为了研究m6A调节器在皮肤衰老中的作用.
- 阐明将m6A修饰与纤维细胞衰老联系起来的分子机制.
- 为了确定参与皮肤衰老的m6A修饰的新目标.
主要方法:
- 蛋白质组学分析以确定与细胞衰老相关的蛋白质.
- 在老化皮肤和纤维细胞中对威尔姆斯瘤1-关联蛋白 (WTAP) 的定量分析.
- 功能性研究涉及人类皮肤纤维细胞 (HDF) 中的基因过度表达和淘汰 (WTAP,ELF3,IRF8).
- m6A依赖机制调查和促进体结合试验.
主要成果:
- WTAP的表达与细胞衰老有显著的相关性,并且在老化皮肤和衰老的HDF中受到上调.
- 过度表达WTAP会诱导衰老,而WTAP倒退则会在HDF中逆转这种情况.
- WTAP以m6A依赖的方式促进ELF3表达;ELF3过度表达拯救了衰老表型.
- 通过直接与IRF8促进体结合,ELF3诱导了与衰老相关的分泌表型 (SASP).
- 在体内,WTAP过度表达加速皮肤衰老并增加衰老.
结论:
- 通过WTAP介导的m6A修饰在调节皮肤衰老方面发挥着至关重要的作用.
- WTAP的目标是ELF3,通过IRF8中介的SASP促进HDF的衰老.
- 这项研究确定了皮肤衰老的新型分子途径,并提出了潜在的治疗点.
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