四川大学‌邓锐杰研究团队利用基因编码活细胞RNA甲基化传感器，对病毒感染的RNA修饰反应进行动态单细胞监测。相关研究成果发表在2025年1月23日出版的《德国应用化学》。

RNA修饰，如腺苷的N6甲基化（m6A），是细胞行为的关键调节因子，并且具有高度的动态性；然而，缺乏用于动态监测活细胞中RNA修饰的工具。

该文中，研究人员开发了一种基因编码的活细胞RNA甲基化传感器，可以在单细胞分辨率下动态监测RNA m6A水平。该传感器使用核定位序列融合的m6A读取通过亲和诱导的细胞质滞留来感测细胞中的RNA m6A。它能够在单细胞水平上同时测量RNA m6A动态和病毒侵袭。

基于单细胞分析工具，研究发现严重急性呼吸系统综合征冠状病毒2型感染提高了宿主细胞RNA m6A水平，宿主细胞中RNA m6A的高水平修饰反过来又促进了病毒感染。

特别是，奥密克戎是严重急性呼吸系统综合征冠状病毒2型的一种变体，具有高感染能力，但在宿主细胞中m6A修饰的促进作用降低。此外，该传感器可以通过测量细胞m6A水平来估计病毒抑制情况，这是为筛选潜在的抗病毒药物而探索的。甲基化传感器可用于在单细胞水平上阐明病原体和宿主细胞表观遗传学之间的相互作用。

附：英文原文

Title: Dynamic, Single-cell Monitoring of RNA Modifications Response to Viral Infection Using a Genetically Encoded Live-cell RNA Methylation Sensor

Author: Ting Zhang, Hao Yang, Quanwei Yu, Yong Zhang, Yue Zhang, Xianglin Zhu, Xuhan Xia, Feng Li, Ruijie Deng

Issue&Volume: 2025-01-23

Abstract: RNA modifications, such as N6-methylation of adenosine (m6A), serve as key regulators of cellular behaviors, and are highly dynamic; however, tools for dynamic monitoring of RNA modifications in live cells are lacking. Here, we develop a genetically encoded live-cell RNA methylation sensor that can dynamically monitor RNA m6A level at single-cell resolution. The sensor senses RNA m6A in cells via affinity-induced cytoplasmic retention using a nuclear location sequence-fused m6A reader. It allows for simultaneously measure RNA m6A dynamics and viral invasion at single-cell level. Based on the single-cell analytical tool, we found that SARS-CoV-2 infection enhances host-cell RNA m6A level, and high-level RNA m6A modification in host cells, in turn, facilitates viral infection. Particularly, Omicron, a variant of SARS-CoV-2, that features as high infection capacity, however, exhibits a reduced facilitation of m6A modification in host cells. In addition, the sensor can estimate viral inhibition via measuring cellular m6A level, that was explored for screening potential antiviral drugs. The methylation sensor can serve for elucidating the interplay between pathogens and host-cell epigenetics at single-cell level.

DOI: 10.1002/anie.202418003

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202418003