4.7 Article

RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation

期刊

DEVELOPMENTAL CELL
卷 58, 期 20, 页码 2112-+

出版社

CELL PRESS
DOI: 10.1016/j.devcel.2023.07.018

关键词

-

向作者/读者索取更多资源

This study identified mutations in the SUPT5H gene associated with beta-thalassemia, highlighting the importance of RNA polymerase II pausing in erythropoiesis. The disruption of pause release was found to affect cell differentiation and proliferation dynamics, resulting in delayed erythroid-specific gene expression.
Controlled release of promoter-proximal paused RNA polymerase II (RNA Pol II) is crucial for gene regulation. However, studying RNA Pol II pausing is challenging, as pause-release factors are almost all essential. In this study, we identified heterozygous loss-of-function mutations in SUPT5H, which encodes SPT5, in individuals with b-thalassemia. During erythropoiesis in healthy human cells, cell cycle genes were highly paused as cells transition from progenitors to precursors. When the pathogenic mutations were recapitulated by SUPT5H editing, RNA Pol II pause release was globally disrupted, and as cells began transitioning from progenitors to precursors, differentiation was delayed, accompanied by a transient lag in erythroid-specific gene expression and cell cycle kinetics. Despite this delay, cells terminally differentiate, and cell cycle phase distributions normalize. Therefore, hindering pause release perturbs proliferation and differentiation dynamics at a key transition during erythropoiesis, identifying a role for RNA Pol II pausing in temporally coordinating the cell cycle and erythroid differentiation.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据