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RNA聚合酶II暂停暂时协调细胞循环的进展和红细胞分化

Danya J Martell¹, Hope E Merens², Alexis Caulier³

¹Department of Genetics, Harvard University, Boston, MA, USA; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Developmental cell

|August 16, 2023

概括

破坏RNA聚合酶II (RNA Pol II) 暂停会延迟细胞周期和红细胞分化. 这项研究揭示了RNA Pol II暂停.

科学领域:

分子生物学分子生物学
基因规则基因规则
红色素质的形成Erythropoiesis

背景情况:

促进体近端暂停RNA聚合酶II (RNA Pol II) 的受控释放对基因调节至关重要.
由于大多数暂停释放因子的基本性质,研究RNA Pol II暂停是困难的.

研究的目的:

调查SUPT5H突变在RNA Pol II暂停中的作用及其对红色素形成的影响.
了解破坏的RNA Pol II暂停释放如何影响细胞周期和分化动态.

主要方法:

在患有β-thalassemia的个体中识别SUPT5H中异构性功能丧失突变.
在人类细胞中通过SUPT5H编辑对病原性突变的总结.
分析RNA Pol II暂停,基因表达,细胞周期动力学和红色素形成过程中的分化.

主要成果:

SUPT5H突变在全球范围内破坏了RNA Pol II暂停释放.
被打断的暂停导致了红状腺分化延迟和红状腺基因表达和细胞周期动力学在原生-前体过渡期间的短暂滞后.
尽管有延迟,终端分化和细胞周期分布最终正常化.

结论:

阻碍RNA Pol II暂停释放扰乱了红色素形成过程中的增殖和分化动态.
RNA Pol II 暂停在细胞周期和红细胞分化的时间协调中起着至关重要的作用.

关键词:

在RNA Pol II中暂停.SPT5 SPT5 SPT5 SPT5 SPT5 SPT5 SPT5 SPT5 SPT5 SPT5 SPT5 在 SUPT5H 中, SUPT5H 包含了细胞循环中的细胞循环.不同化的差异化差异化.红色素质的人类形成.血红蛋白血红蛋白是一个人类遗传变异人类遗传变异转录规则转录规则转录规则

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