Assistant Professor Khalifa University, Abu Dhabi, United Arab Emirates
Abstract: Vault RNAs (vtRNAs) are small non-coding RNAs implicated in cellular homeostasis, stem cell regulation, and gene expression. Previous studies have shown that vtRNA1-1 is methylated by NSUN2, regulating its cleavage into small vault RNAs (svRNAs), which function as microRNA-like regulatory RNAs. Here, we demonstrate that Drosha, a key enzyme in miRNA biogenesis, processes unmethylated vtRNA1-1 into svRNA1, while Dicer is dispensable for this process. Using pull-down assays and small RNA sequencing, we show that Drosha preferentially binds unmethylated vtRNA1-1, facilitating svRNA1 production. Functional studies reveal that svRNA1 promotes epidermal stem cell differentiation by targeting epithelial-mesenchymal transition (EMT) pathways, as evidenced by reduced cell migration and upregulation of differentiation markers. Gene ontology analysis identifies svRNA1 targets involved in chromatin remodeling, epigenetic regulation, and neural and germ cell differentiation, linking svRNA1 to NSUN2-mediated pathways. These findings uncover a novel role for Drosha in vtRNA1-1 processing and highlight svRNA1 as a key regulator of stem cell differentiation, offering insights into the interplay between RNA modifications, non-coding RNAs, and cellular plasticity.
Funding Source: Khalifa University of Science and Technology Competitive Internal Research Award RIG-2023-116 Khalifa University of Science and Technology Competitive Internal Research Award CIRA-ADEK 8474000304
