英国牛津大学Neil Brockdorff、Lothar Schermelleh等研究人员合作利用时间分辨的结构照明显微镜揭示Xist RNA扩散的关键原理。相关论文于2021年6月11日发表于国际学术期刊《科学》上。

为了阐明X失活的特异性转录物（Xist）RNA顺式限制的机制，研究人员建立了一种连续双色标记、超分辨率成像方法来随时间追踪单个Xist RNA分子，这能够定义传播的基本参数。研究人员展示了将Xist RNA合成和降解联系起来的反馈机制，以及先前和新合成的Xist RNA分子之间的意外物理耦合。

此外，研究人员发现蛋白质SPEN（Xist 介导的基因沉默的关键因素）在Xist RNA定位、稳定性和耦合行为中具有独特的功能。这些结果为理解Xist RNA的独特动态特性提供了见解。

据了解，Xist RNA通过沿着转录它的染色体顺式扩散并招募染色质修饰物来沉默基因转录，从而指导哺乳动物中X染色体失活的过程。

附：英文原文

Title: Time-resolved structured illumination microscopy reveals key principles of Xist RNA spreading

Author: Lisa Rodermund, Heather Coker, Roel Oldenkamp, Guifeng Wei, Joseph Bowness, Bramman Rajkumar, Tatyana Nesterova, David Miguel Susano Pinto, Lothar Schermelleh, Neil Brockdorff

Issue&Volume: 2021/06/11

Abstract: X-inactive specific transcript (Xist) RNA directs the process of X chromosome inactivation in mammals by spreading in cis along the chromosome from which it is transcribed and recruiting chromatin modifiers to silence gene transcription. To elucidate mechanisms of Xist RNA cis-confinement, we established a sequential dual-color labeling, super-resolution imaging approach to trace individual Xist RNA molecules over time, which enabled us to define fundamental parameters of spreading. We demonstrate a feedback mechanism linking Xist RNA synthesis and degradation and an unexpected physical coupling between preceding and newly synthesized Xist RNA molecules. Additionally, we find that the protein SPEN, a key factor for Xist-mediated gene silencing, has a distinct function in Xist RNA localization, stability, and coupling behaviors. Our results provide insights toward understanding the distinct dynamic properties of Xist RNA.

DOI: 10.1126/science.abe7500

Source: https://science.sciencemag.org/content/372/6547/eabe7500