Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Cell Biochem. 2018 Apr;119(4):3174-3182. doi: 10.1002/jcb.26472. Epub 2017 Dec 26.
Rn7SK-mediated global transcriptional regulation, key function of this small nuclear RNA (snRNA), is mediated by inhibition of the positive transcription elongation factor b (P-TEFb). Recently, we have identified a potential anti-proliferative and tumor-suppressive function of Rn7SK. However, its possible regulatory role in development and cell programming has not been investigated so far. Here, we examined transcriptional levels of Rn7SK in different mouse organs. Interestingly, an increased expression level of the RNA was observed in the brain. Furthermore, we could demonstrate that Rn7SK has a dynamic expression pattern during brain development from embryo to adult: 7SK snRNA expression was particularly high at embryonic day (E) 18.5 and adult stages, while a low level of this non-coding RNA was detected at E11.5. Moreover, a decreased transcription level was identified in proliferating progenitors whereas a strong upregulation of Rn7SK was observed during neural differentiation in vivo. Similar to the in vivo situation, in vitro neuronal differentiation experiments employing embryonic stem cells (ESCs) demonstrated the same expression pattern of 7SK with high expression levels in differentiating neurons. Neuronal differentiation of ESCs was compromised when we knocked down Rn7SK, indicating an important role of 7SK in the acquisition of a neural fate.
Rn7SK 介导的全球转录调控是这种小核 RNA(snRNA)的关键功能,它通过抑制正转录延伸因子 b(P-TEFb)来介导。最近,我们已经确定了 Rn7SK 具有潜在的抗增殖和肿瘤抑制功能。然而,其在发育和细胞编程中的可能调节作用迄今尚未得到研究。在这里,我们检查了不同小鼠器官中 Rn7SK 的转录水平。有趣的是,在大脑中观察到 RNA 的表达水平增加。此外,我们能够证明 Rn7SK 在大脑发育过程中具有动态表达模式:从胚胎到成年,7SK snRNA 的表达水平特别高,而在 E11.5 时则检测到这种非编码 RNA 的低水平。此外,在增殖祖细胞中鉴定到转录水平降低,而在体内神经分化过程中观察到 Rn7SK 的强烈上调。与体内情况相似,在胚胎干细胞(ESCs)中进行的体外神经元分化实验证明了 7SK 的相同表达模式,分化神经元中的表达水平较高。当我们敲低 Rn7SK 时,ESCs 的神经元分化受到损害,这表明 7SK 在获得神经命运中起着重要作用。