M6A RNA Methylation-Mediated TUG1 Stability Maintains Mitochondrial Homeostasis during Kidney Aging by Epigenetically Regulating PGC1-α Expression

• DOI: 10.1089/ars.2024.0631
• Publication Date: 2024-08-13T06:19:13Z
• Authors: Yonghong Zhu; Bowen Yang; Suyun Chen; Guanqing Chen; Xiaobian Zeng; Hui Min; Li Xu
• Keywords: N6-Methyladenosine

Aging is a significant risk factor for the increased incidence of acute kidney injury and chronic disease, posing challenges to global public health. The role N6-methyladenosine (m6A) in development disease has been reported, but regulatory mechanism m6A aging remains unclear. In this study, we identified long non-coding RNA (lncRNA), called TUG1, which exhibited significantly decreased level modification human aged through m6A-lncRNA epitranscriptome microarray. Bioinformatics analysis machine learning predicted that TUG1 formed potentially strong interaction with PGC1-α. RIP ChIP supported promoted proliferator-activated receptor γ coactivator-1α (PGC1-α) expression by directly interact its TBE region, thereby impacting mitochondrial quality control, cellular senescence renal fibrosis. Silencing methylase METTL14 or reader protein IGF2BP2 resulted weakened stability LncRNA contributing an imbalance control. Our study demonstrated was mediated IGF2BP2-dependent manner, modulate homeostasis direct targeting PGC-1α. These findings provide new perspective on potential therapeutic targets aging.