浙江大学钱鹏旭等研究人员合作发现，相分离能力强的FBL可促进急性髓性白血病的早期pre-rRNA加工和翻译。2024年5月14日出版的《自然—细胞生物学》杂志发表了这项成果。

据了解，RNA结合蛋白（RBP）在AML这一致命疾病中起着关键作用。虽然在AML中发现了特异性相分离功能的RBP，但它们的凝聚物形成对AML白血病生成的影响以及抑制相分离的治疗潜力尚未得到充分探索。

附：英文原文

Title: Phase separation-competent FBL promotes early pre-rRNA processing and translation in acute myeloid leukaemia

Author: Yang, Lin, Zhang, Zhaoru, Jiang, Penglei, Kong, Delin, Yu, Zebin, Shi, Danrong, Han, Yingli, Chen, Ertuo, Zheng, Weiyan, Sun, Jie, Zhao, Yanmin, Luo, Yi, Shi, Jimin, Yao, Hangping, Huang, He, Qian, Pengxu

Issue&Volume: 2024-05-14

Abstract: RNA-binding proteins (RBPs) are pivotal in acute myeloid leukaemia (AML), a lethal disease. Although specific phase separation-competent RBPs are recognized in AML, the effect of their condensate formation on AML leukaemogenesis, and the therapeutic potential of inhibition of phase separation are underexplored. In our in vivo CRISPR RBP screen, fibrillarin (FBL) emerges as a crucial nucleolar protein that regulates AML cell survival, primarily through its phase separation domains rather than methyltransferase or acetylation domains. These phase separation domains, with specific features, coordinately drive nucleoli formation and early processing of pre-rRNA (including efflux, cleavage and methylation), eventually enhancing the translation of oncogenes such as MYC. Targeting the phase separation capability of FBL with CGX-635 leads to elimination of AML cells, suggesting an additional mechanism of action for CGX-635 that complements its established therapeutic effects. We highlight the potential of PS modulation of critical proteins as a possible therapeutic strategy for AML.

DOI: 10.1038/s41556-024-01420-z

Source: https://www.nature.com/articles/s41556-024-01420-z