NONO蛋白调节非经典DNA结构：对昼夜节律基因和DNA损伤的影响。
The NONO protein regulates nonclassical DNA structure: Effects on circadian genes and DNA damage.
作者信息
Moriggi Ermanno, Pisteljic Melissa, Rosi-Andersen Alex, Opitz Lennart, Azzi Abdelhalim, Brown Steven A
机构信息
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Experimental Psychopathology and Psychotherapy, Department of Psychology, University of Zurich, Zurich, Switzerland.
出版信息
iScience. 2025 Apr 11;28(5):112408. doi: 10.1016/j.isci.2025.112408. eCollection 2025 May 16.
The DBHS protein family of Nono, PSPC1, and SFPQ regulates diverse aspects of RNA metabolism. Whether these proteins share similar functions is currently unknown. In mouse embryonic fibroblasts (MEFs), we observed around 2000 circadian and non-circadian genes regulated by Nono and PSPC1, with only 35% in common. Considering specifically circadian genes, up- or downregulation by Nono and PSPC1 depends mainly on the gene phase. We postulated a regulatory role of Nono on R-loops, the class of non-B DNA structures that form during transcription. We confirmed this by showing a broad effect of Nono on genome-wide R-loop homeostasis. Interestingly, the R-loop regulation by Nono occurs in a time-of-day dependent manner among the circadian genes. Moreover, we showed a protective role of Nono in a DNA damage cellular model that involves R-loop accumulation. Further studies are required to understand the circadian regulation of R-loops and their implications on gene regulation and disease.
由Nono、PSPC1和SFPQ组成的DBHS蛋白家族调节RNA代谢的多个方面。目前尚不清楚这些蛋白是否具有相似的功能。在小鼠胚胎成纤维细胞（MEF）中，我们观察到约2000个受Nono和PSPC1调节的昼夜节律和非昼夜节律基因，其中只有35%是相同的。具体考虑昼夜节律基因，Nono和PSPC1对其上调或下调主要取决于基因相位。我们推测Nono对R环具有调节作用，R环是转录过程中形成的一类非B型DNA结构。我们通过证明Nono对全基因组R环稳态具有广泛影响来证实了这一点。有趣的是，Nono对R环的调节在昼夜节律基因中以时间依赖性方式发生。此外，我们在涉及R环积累的DNA损伤细胞模型中显示了Nono的保护作用。需要进一步研究来了解R环的昼夜节律调节及其对基因调控和疾病的影响。
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