Yang Qianqian, Yu Xiaochun
School of Life Sciences, Fudan University, Shanghai, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province, China.
Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province, China.
J Biol Chem. 2025 Aug 16:110609. doi: 10.1016/j.jbc.2025.110609.
NSD2 (nuclear receptor binding SET domain protein 2) gene encodes a short isoform, REIIBP (interleukin-5 [IL-5] response element II binding protein), via alternative transcription initiation. It is particularly overexpressed in t(4;14)+ multiple myeloma (MM). However, the biological functions of REIIBP remain elusive. Here, we show that REIIBP localizes at the dense fibrillar component (DFC) of the nucleolus. The disordered regions of REIIBP recognize pre-ribosomal RNA (pre-rRNA), which mediates the nucleolar localization of REIIBP. Proteomic analyses reveal that REIIBP is associated with many pre-rRNA processing factors, and mediates lysine methylation on a set of pre-rRNA processing factors. Moreover, REIIBP dysregulates pre-rRNA processing, mediated by both disordered regions and the SET domain, and ultimately affects ribosome biogenesis. Collectively, these findings uncover the role of REIIBP in the regulation of ribosome biogenesis, which may drive the pathological process in MM.
NSD2（核受体结合SET结构域蛋白2）基因通过可变转录起始编码一种短异构体REIIBP（白细胞介素-5[IL-5]反应元件II结合蛋白）。它在t(4;14)+多发性骨髓瘤（MM）中特别过度表达。然而，REIIBP的生物学功能仍然不清楚。在这里，我们表明REIIBP定位于核仁的致密纤维成分（DFC）。REIIBP的无序区域识别前核糖体RNA（pre-rRNA），这介导了REIIBP的核仁定位。蛋白质组学分析表明，REIIBP与许多前rRNA加工因子相关，并介导一组前rRNA加工因子上的赖氨酸甲基化。此外，REIIBP通过无序区域和SET结构域介导前rRNA加工失调，最终影响核糖体生物发生。总的来说，这些发现揭示了REIIBP在核糖体生物发生调控中的作用，这可能推动MM的病理过程。
