RBFOX2 识别了 N6 - - 甲基氨酸以抑制转录并阻止骨髓性白血病分化
Xiaoyang Dou1,2, Yu Xiao1,2, Chao Shen3,4,5
1Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.
Nature cell biology
|August 28, 2023
概括
RBFOX2通过m6A将甲基转移酶复合体 (MTC) 引入与染色质相关的RNA (caRNAs),调节基因转录和染色质. 这一途径对髓性白血病至关重要,提供了潜在的治疗点.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 在RNA生物学,RNA生物学.
- 癌症生物学 癌症生物学
背景情况:
- 在染色质关联RNAs (caRNAs) 上的N6-甲基氨酸 (m6A) 甲基化影响染色质状态和转录.
- 没有充分了解RNA甲基转移酶复合体 (MTC) 到特定基因组位置的招募机制.
研究的目的:
- 阐明MTC招募到基因组位置的机制.
- 为了确定参与m6A沉积在caRNAs上的染色质因子.
- 为了研究这种途径在髓性白血病中的作用.
主要方法:
- 确定RBFOX2作为caRNAs上的m6A结合蛋白.
- 同免疫沉试验用于研究蛋白质相互作用 (RBFOX2,RBM15,YTHDC1,PRC2).
- 在急性髓性白血病细胞中进行功能测试,以评估RBFOX2在干细胞增殖,分化和自我更新中的作用.
主要成果:
- RBFOX2在caRNA上识别m6A,并将RBM15 (一个MTC组件) 招募到促进器关联的RNA中.
- RBM15与YTHDC1相互作用,并将PRC2招募到与RBFOX2结合的位置,导致染色质沉默和抑制转录.
- 在髓性白血病中,RBFOX2/m6A/RBM15/YTHDC1/PRC2轴至关重要;RBFOX2的下调抑制白血病细胞存活并促进分化.
结论:
- 已经确定了m6A MTC招募和m6A沉积在caRNA上的新途径.
- 这一途径调节了局部选择性染色质调节和转录抑制.
- 通过RBFOX2介导的途径对于急性髓性白血病的维持至关重要,并具有潜在的治疗意义.
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