Small 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. Here, 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. The 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.

中文翻译：

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jouvence，一种参与控制细胞增殖的新型人类snoRNA

小核仁RNA（snoRNA）是从古细菌到哺乳动物保守的非编码RNA。它们在核仁中与蛋白质结合形成小核仁核糖核蛋白（snoRNPs）。它们修饰核糖体RNA，例如将尿苷转化为假尿苷的H / ACA盒。在人类中，多种病理已与snoRNA相关，据报道，几种snoRNA参与了许多癌症过程。最近，在果蝇中发现了一种新的H / ACA盒snoRNA，名为jouvence，已证明与肠道动态平衡有关。由于snoRNA在结构和功能上都通过进化得到保守，因此在人类中已鉴定出柔韧性直向同源物。RT-PCR显示表达出柔韧性，表明它可能起作用。这些结果表明假说可能具有相似的功能，包括增加人类的健康寿命。在这里，我们报告了人类snoRNA柔韧性的特征，该特征尚未在基因组中进行注释。我们表明，其过表达显着刺激细胞增殖，无论是在各种稳定的癌细胞系中还是在原代细胞中。相比之下，其被siRNA击倒会导致相反的表型，即细胞增殖迅速下降。转录组学分析（RNA-Seq）表明，过激表达的过表达导致细胞的去分化特征。相反，抑制柔韧性使核糖体生物发生和剪接体中涉及的基因的表达水平显着下降。159个核苷酸的单个和短非编码RNA的过表达（snoRNA柔韧性）似乎足以使细胞重新定向至干性，而其耗竭则阻止细胞增殖。在这种情况下，我们推测，似乎是非典型的H / ACA snoRNA的过表达过表达可能是对抗衰老的有害作用的新工具，相反，被siRNA抑制的衰老可能代表了一种新的手段。癌症治疗方法。