Cellular senescence is an irreversible state of cell-cycle arrest induced by various stresses, including aberrant oncogene activation, telomere shortening, and DNA damage. Through a genome-wide screen, we discovered a conserved small nucleolar RNA (snoRNA), SNORA13, that is required for multiple forms of senescence in human cells and mice. Although SNORA13 guides the pseudouridylation of a conserved nucleotide in the ribosomal decoding center, loss of this snoRNA minimally impacts translation. Instead, we found that SNORA13 negatively regulates ribosome biogenesis. Senescence-inducing stress perturbs ribosome biogenesis, resulting in the accumulation of free ribosomal proteins (RPs) that trigger p53 activation. SNORA13 interacts directly with RPL23, decreasing its incorporation into maturing 60S subunits and, consequently, increasing the pool of free RPs, thereby promoting p53-mediated senescence. Thus, SNORA13 regulates ribosome biogenesis and the p53 pathway through a non-canonical mechanism distinct from its role in guiding RNA modification. These findings expand our understanding of snoRNA functions and their roles in cellular signaling.

细胞衰老是由各种应激引起的细胞周期停滞的不可逆状态，包括异常癌基因激活、端粒缩短和 DNA 损伤。通过全基因组筛选，我们发现了一种保守的小核仁 RNA (snoRNA)，SNORA13，它是人类细胞和小鼠多种形式衰老所必需的。尽管 SNORA13 指导核糖体解码中心保守核苷酸的假尿苷化，但这种 snoRNA 的丢失对翻译的影响微乎其微。相反，我们发现 SNORA13 负向调节核糖体生物发生。诱导衰老的应激会扰乱核糖体生物发生，导致游离核糖体蛋白 (RP) 的积累，从而触发 p53 激活。 SNORA13 直接与 RPL23 相互作用，减少其与成熟 60S 亚基的结合，从而增加游离 RP 池，从而促进 p53 介导的衰老。因此，SNORA13 通过不同于其引导 RNA 修饰作用的非规范机制来调节核糖体生物合成和 p53 途径。这些发现拓展了我们对 snoRNA 功能及其在细胞信号传导中的作用的理解。