Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations.
Alpha-satellite RNA transcripts are repressed by centromere-nucleolus associations.
复制标题
α-卫星RNA转录本被Centromere-Nucleolus关联抑制。
DOI：
10.7554/elife.59770
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发表时间：
2020-11-11
期刊：
影响因子：
7.7
通讯作者：
Cheeseman IM
中科院分区：
文献类型：
--
作者：
Bury L;Moodie B;Ly J;McKay LS;Miga KH;Cheeseman IM
虽然最初被认为是沉默的染色体区域，但着丝粒却被活跃地转录。然而，着丝粒衍生的RNA的行为和贡献仍然不清楚。在这里，我们使用单分子荧光原位杂交（smFISH）来检测完整人类细胞中的α-卫星RNA转录本。我们发现，α-卫星RNA-smFISH焦点水平在细胞系和细胞周期中各不相同，但不与着丝粒相关，显示与其他长非编码RNA一致的定位。α-卫星表达通过RNA聚合酶II依赖的转录发生，但不需要建立着丝粒或细胞分裂组件。相反，我们的工作暗示着丝粒-核仁相互作用抑制α-卫星表达。核仁定位的着丝粒的分数与跨细胞系的α-卫星转录物水平负相关，并且当核仁被破坏时，转录物水平显著增加。通过着丝粒-核仁接触控制α-卫星转录物提供了在不同细胞状态和条件下调节着丝粒转录和染色质动力学的机制。
Although originally thought to be silent chromosomal regions, centromeres are instead actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA-smFISH foci levels vary across cell lines and over the cell cycle, but do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Alpha-satellite expression occurs through RNA polymerase II-dependent transcription, but does not require established centromere or cell division components. Instead, our work implicates centromere–nucleolar interactions as repressing alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels across cell lines and transcript levels increase substantially when the nucleolus is disrupted. The control of alpha-satellite transcripts by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.