Jouvence, a new human snoRNA involved in the control of cell proliferation

Abstract

BackgroundSmall nucleolar RNAs (snoRNAs) are non-coding RNAs that are conserved from archaebacteria to mammals. They are associated in the nucleolus, with proteins to form small nucleolar ribonucleoprotein (snoRNPs). They modify ribosomal RNAs, for example, the H/ACA box that converts uridine to pseudouridine. In humans, various pathologies have been associated with snoRNAs, and several snoRNAs have been reported to participate in many cancer processes. Recently, a new H/ACA box snoRNA named jouvence has been identified in Drosophila and has been shown to be involved in lifespan determination in relation to gut homeostasis. Because snoRNAs are conserved through evolution, both structurally and functionally, a jouvence orthologue has been identified in humans. RT-PCR has revealed that jouvence is expressed, suggesting that it might be functional. These results suggest the hypothesis that jouvence may display similar functions, including increasing the healthy lifespan in humans.ResultsHere, we report the characterization of the human snoRNA jouvence, which has not yet been annotated in the genome. We show that its overexpression significantly stimulates cell proliferation, both in various stable cancerous cell lines as well as in primary cells. By contrast, its knockdown by siRNA leads to the opposite phenotype, a rapid decrease in cell proliferation. Transcriptomic analysis (RNA-Seq) revealed that the overexpression of jouvence leads to a dedifferentiation signature of the cells. Conversely, the knockdown of jouvence led to a striking decrease in the expression levels of genes involved in ribosome biogenesis and the spliceosome.ConclusionThe overexpression of a single and short non-coding RNA of 159 nucleotides, the snoRNA-jouvence, seems to be sufficient to reorient cells toward stemness, while its depletion blocks cell proliferation. In this context, we speculate that the overexpression of jouvence, which appears to be a non-canonical H/ACA snoRNA, could represent a new tool to fight against the deleterious effects of aging, while inversely, its knockdown by siRNA could represent a new approach in cancer therapy.