CDKAL1 dysfunction impairs lysine codon translation in podocytes and accelerates chronic kidney disease - PubMed
3 hours ago
- #Chronic Kidney Disease
- #tRNA Modification
- #CDKAL1
- CDKAL1 dysfunction impairs tRNA modification, specifically ms2t6A generation in tRNALysUUU.
- CDKAL1 variants are risk factors for CKD and type 2 diabetes, with CKD progression shown independently of diabetes in studies.
- Systemic and podocyte-specific Cdkal1 knockout in mice leads to CKD phenotypes, especially under increased kidney burden.
- Cdkal1 deficiency reduces lysine-codon translation and lysine-rich protein levels in podocytes, impairing functions like cell migration.
- Overexpression of lysine-rich protein CD2AP partially reverses adverse effects in Cdkal1-knockout podocytes.
- Findings introduce 'tRNA modopathy' as a concept in kidney disease, linking defective tRNA modification to CKD progression.