Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, The USTC RNA Institute, Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Life Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, Anhui, 230027, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Nat Commun. 2024 Aug 23;15(1):7256. doi: 10.1038/s41467-024-51693-z.
Environmental stimuli not only alter gene expression profiles but also induce structural changes in cells. How distinct nuclear bodies respond to cellular stress is poorly understood. Here, we identify a subnuclear organelle named the nucleolar stress body (NoSB), the formation of which is induced by the inhibition of rRNA transcription or inactivation of rRNA processing and maturation in C. elegans. NoSB does not colocalize with other previously described subnuclear organelles. We conduct forward genetic screening and identify a bZIP transcription factor, named nucleolar stress response-1 (NOSR-1), that is required for NoSB formation. The inhibition of rRNA transcription or inactivation of rRNA processing and maturation increases nosr-1 expression. By using transcriptome analysis of wild-type animals subjected to different nucleolar stress conditions and nosr-1 mutants, we identify that the SR-like protein NUMR-1 (nuclear localized metal responsive) is the target of NOSR-1. Interestingly, NUMR-1 is a component of NoSB and itself per se is required for the formation of NoSB. We conclude that the NOSR-1/NUMR-1 axis likely responds to nucleolar stress and mediates downstream stress-responsive transcription programs and subnuclear morphology alterations in C. elegans.
环境刺激不仅改变基因表达谱，还诱导细胞的结构变化。不同的核体如何响应细胞应激尚不清楚。在这里，我们鉴定了一种亚核细胞器，命名为核仁应激体（NoSB），其形成是由 rRNA 转录的抑制或 rRNA 加工和成熟的失活在秀丽隐杆线虫中诱导的。NoSB 与其他先前描述的亚核细胞器不共定位。我们进行正向遗传筛选，鉴定了一种 bZIP 转录因子，命名为核仁应激反应-1（NOSR-1），它是 NoSB 形成所必需的。rRNA 转录的抑制或 rRNA 加工和成熟的失活会增加 nosr-1 的表达。通过对野生型动物在不同核仁应激条件下和 nosr-1 突变体中的转录组分析，我们确定了 SR 样蛋白 NUMR-1（核定位金属响应）是 NOSR-1 的靶标。有趣的是，NUMR-1 是 NoSB 的一个组成部分，其本身就需要 NoSB 的形成。我们得出结论，NOSR-1/NUMR-1 轴可能对核仁应激作出反应，并介导秀丽隐杆线虫下游应激反应转录程序和亚核形态改变。
