4.8 Article

Four-dimensional nuclear speckle phase separation dynamics regulate proteostasis

期刊

SCIENCE ADVANCES
卷 8, 期 1, 页码 -

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abl4150

关键词

-

资金

  1. National Institute of Health [DP2GM140924, T32AG021885, P30DK120531]
  2. American Diabetes Association [1-18-JDF-025]
  3. EW Biomedical Scholars Program [00033066]
  4. National Science Foundation [CHE-1944973]

向作者/读者索取更多资源

This study identified a cell-autonomous 12-hour ultradian rhythm mechanism in mammals that is separate from the 24-hour circadian clock and the cell cycle. By modulating the temporal dynamics of proteostasis, the nuclear speckle LLPS may represent a previously unidentified therapeutic target for pathologies associated with dysregulated proteostasis.
Phase separation and biorhythms control biological processes in the spatial and temporal dimensions, respectively, but mechanisms of four-dimensional integration remain elusive. Here, we identified an evolutionarily conserved XBP1s-SON axis that establishes a cell-autonomous mammalian 12-hour ultradian rhythm of nuclear speckle liquid-liquid phase separation (LLPS) dynamics, separate from both the 24-hour circadian clock and the cell cycle. Higher expression of nuclear speckle scaffolding protein SON, observed at early morning/early afternoon, generates diffuse and fluid nuclear speckles, increases their interactions with chromatin proactively, transcriptionally amplifies the unfolded protein response, and protects against proteome stress, whereas the opposites are observed following reduced SON level at early evening/late morning. Correlative Son and proteostasis gene expression dynamics are further observed across the entire mouse life span. Our results suggest that by modulating the temporal dynamics of proteostasis, the nuclear speckle LLPS may represent a previously unidentified (chrono)-therapeutic target for pathologies associated with dysregulated proteostasis.

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

4.8
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