里克索姆RNA降解有助于抑制Polycomb目标基因
Haining Zhou1, Chad B Stein2, Tiasha A Shafiq1
1Howard Hughes Medical Institute, Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nature
|March 31, 2022
概括
瑞克索姆 (RIX1复合体) 通过降解由酵母保存的可选异质染色体的新生RNA来帮助抑制人体细胞中的Polycomb目标.
科学领域:
- 表观遗传学和基因调控
- 核糖核酸生物学
- 染色体结构
背景情况:
- 多抑制复合体 (PRC1和PRC2) 建立可选的异染色体并使发育基因沉默.
- 在裂变酵母中,涉及体 (RIX1复合体) 的RNA衰变途径对异性染色质的维持至关重要.
- 在哺乳动物的异染色体稳定性中RNA降解的作用以前是未知的.
研究的目的:
- 研究类组 (RIX1复合体) 在哺乳动物异染色体形成和稳定性的作用.
- 确定RNA降解是否有助于人类细胞中的Polycomb抑制复合物的功能.
主要方法:
- 通过基因操纵来消耗体和多体蛋白质.
- 染色体免疫沉以评估基因促进者的蛋白质丰富.
- 对RNA聚合酶活性和基因表达的分析.
- 局部定向的突变发生以破坏蛋白质与蛋白质的相互作用.
主要成果:
- 它与人体PRC复合体结合,并局部化为Polycomb目标基因促进体.
- 基因或多基因的枯竭导致基因的RNA聚合酶积累增加.
- 在RING1B中发生的突变会破坏PRC1- 瑞克索姆的相互作用,并影响基因沉默.
- 基因和XRN2活动对于Polycomb介导的基因沉默至关重要.
结论:
- 在人体细胞的选择性异质染色体中,体在RNA降解中起着保留作用.
- 在Polycomb介导的基因沉默过程中,新生RNA的基因组分解是必需的.
- 通过PRC1直接招募到染色体对于异性染色体的稳定性至关重要.
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