IGF2BP3/NCBP1 complex inhibits renal tubular senescence through regulation of CDK6 mRNA stability.
Abstract
Renal aging and the subsequent rise in kidney-related diseases are attributed to senescence in renal tubular epithelial cells (RTECs). Our study revealed that the abnormal expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader of RNA N6-methyladenosine, is critically involved in cisplatin-induced renal tubular senescence. In cisplatin-induced senescence of RTECs, the promoter activity and transcription of IGF2BP3 is markedly suppressed. It was due to the down regulation of MYC proto-oncogene (MYC), which regulates IGF2BP3 transcription by binding to the putative site at 1852-1863 of the IGF2BP3 promoter. Overexpression of IGF2BP3 ameliorated cisplatin-induced renal tubular senescence in vitro. Mechanistic studies revealed that IGF2BP3 inhibits cellular senescence in RTECs by enhancing cyclin-dependent kinase 6 (CDK6) mRNA stability and increasing its expression. The inhibition effect of IGF2BP3 on tubular senescence is partially reversed by the knockdown of CDK6. Further, IGF2BP3 recruits nuclear cap binding protein subunit 1 (NCBP1) and inhibits CDK6 mRNA decay, by recognizing m
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Research summary
The paper investigates the role of IGF2BP3 in renal tubular senescence, which is a process related to aging and age-related diseases. It explores a mechanism that could potentially mitigate cellular senescence, thus addressing a root cause of aging at the cellular level. However, while the findings are solid and contribute to understanding the molecular pathways involved in renal aging, the impact is limited as it primarily focuses on a specific cellular mechanism without broader implications for longevity or lifespan extension.
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