Benítez Belén, Stortz Martin, De Rossi María Cecilia, Presman Diego Martín, Levi Valeria
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
iScience. 2025 May 15;28(6):112678. doi: 10.1016/j.isci.2025.112678. eCollection 2025 Jun 20.
Several proteins necessary for mRNA production concentrate in intranuclear condensates, which are proposed to affect transcriptional output. The glucocorticoid receptor (GR) is a ligand-activated transcription factor that regulates the expression of hundreds of genes relevant to many physiological and pathological processes. As with all members of the steroid receptor family, GR forms condensates of unknown function. Here, we examine whether GR condensates are involved in transcription regulation using Airyscan super-resolution microscopy and nano-antibodies targeting initiation and elongating states of RNA polymerase II (Pol2). We observed subpopulations of GR condensates colocalizing with initiating and, surprisingly, elongating Pol2 foci. The analysis of GR mutants with different transcriptional outputs suggests a correlation between condensate formation capability and transcription initiation. Moreover, the number of GR molecules within initiation and elongation condensates appears to be linked to transcriptional activity. Taken together, our data suggests an involvement of GR condensates in transcription initiation and elongation.
几种mRNA产生所必需的蛋白质聚集在核内凝聚物中，有人认为这些凝聚物会影响转录输出。糖皮质激素受体（GR）是一种配体激活的转录因子，可调节数百种与许多生理和病理过程相关的基因的表达。与类固醇受体家族的所有成员一样，GR会形成功能未知的凝聚物。在这里，我们使用Airyscan超分辨率显微镜和靶向RNA聚合酶II（Pol2）起始和延伸状态的纳米抗体，研究GR凝聚物是否参与转录调控。我们观察到GR凝聚物的亚群与起始Pol2焦点共定位，令人惊讶的是，还与延伸Pol2焦点共定位。对具有不同转录输出的GR突变体的分析表明，凝聚物形成能力与转录起始之间存在相关性。此外，起始和延伸凝聚物中的GR分子数量似乎与转录活性有关。综上所述，我们的数据表明GR凝聚物参与转录起始和延伸。
