Comprehensive landscape of RNA N6-methyladenosine modification in lens epithelial cells from normal and diabetic cataract

Abstract

To gain more insight into the mechanism of cataract formation from the perspective of epigenetics in the diabetic population, lens epithelium from diabetic cataract patients and healthy donors were collected separately and analyzed for N6-methyladenosine (m6A)-modified RNA using methylated RNA immunoprecipitation sequencing (MeRIP-Seq). Subsequently, differential expression analysis was performed on m6A-regulated messenger RNA (mRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA), followed by functional annotation using the Gene Ontology (GO) database. Furthermore, analysis of single-cell data of lens complemented the intrinsic association and cellular heterogeneity of cataract and m6A regulators. In this study, both the global expression levels and peak intensity of m6A-tagged RNAs were increased in patients with diabetic cataract. And we noted multiple core enzymes were upregulated in the diabetic cataract (DC) samples. Besides, single-cell RNA sequencing analysis of the lens revealed the heterogeneous expression of RNA m6A regulators across different cell types, and we noted that the early fiber cell cluster was also closely associated with the onset of cataract and m6A modification. The results comprehensively revealed the dynamic modification landscape of m6A on mRNA, circRNA, and lncRNA, which might provide valuable resources for future studies of the pathogenesis of DCs.