M6A RNA甲基化介导的TUG1稳定性通过表观遗传调控PGC1-α的表达,在肾脏衰老过程中维持线粒体稳态。

IF 5.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yonghong Zhu, Bowen Yang, Suyun Chen, Guanqing Chen, Xiaobian Zeng, Hui Min, Li Xu
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引用次数: 0

摘要

衰老是急性肾损伤和慢性肾病发病率增加的一个重要风险因素,给全球公共卫生带来了重大挑战。N6-甲基腺苷(m6A)在慢性肾脏病发病中的作用已有报道,但m6A在肾脏衰老中的调控机制仍不清楚。在这项研究中,我们通过 m6A-lncRNA 表转录组芯片发现了一种名为 TUG1 的长非编码 RNA(lncRNA),它在人类衰老肾脏中的 m6A 修饰水平显著下降。生物信息学分析和机器学习预测,TUG1可能与PGC1-α形成强相互作用。RIP和ChIP分析证实,TUG1通过与其TBE区直接相互作用,促进了增殖激活受体γ辅激活剂-1α(PGC1-α)的表达,从而影响线粒体质量控制、细胞衰老和肾脏纤维化。沉默 RNA m6A 甲基化酶 METTL14 或阅读蛋白 IGF2BP2 会削弱 LncRNA TUG1 的稳定性,导致线粒体质量控制失衡。我们的研究表明,METTL14以IGF2BP2依赖的方式介导了TUG1的m6A修饰和稳定性,并通过直接靶向PGC-1α调节肾脏衰老过程中的线粒体稳态。这些发现为肾脏衰老的潜在治疗靶点提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
M6A RNA Methylation-Mediated TUG1 Stability Maintains Mitochondrial Homeostasis during Kidney Aging by Epigenetically Regulating PGC1-α Expression.
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来源期刊
Antioxidants & redox signaling
Antioxidants & redox signaling 生物-内分泌学与代谢
CiteScore
14.10
自引率
1.50%
发文量
170
审稿时长
3-6 weeks
期刊介绍: Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology
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