RH3 enhances antiviral defense by facilitating small RNA loading into Argonaute 2 at endoplasmic reticulum–chloroplast membrane contact sites

作者：Juan Huang, Juan Du, Yan Liu, Lu Lu, Yanzhuo Xu, Jianfei Shi, Qing Liu, Qi Li, Yang Liu, Yaqiu Chen, Meng Du, Yi-Ming Zhao, Lanqing Huo, Weiran Wang, Chenxi Ding, Liya Wei, Jianguo Wu, Yao‐Wu Yuan, Jinfeng Chen, Ruixi Li, Feng Cui, Xiaoming Zhang · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-57296-6 · 被引用次数：7 · 研究领域：Photosynthetic Processes and Mechanisms、RNA modifications and cancer、Plant Virus Research Studies

While RNA silencing is crucial for plant resistance against viruses, the cellular connections between RNA silencing and antiviral responses in plants remain poorly understood. In this study, we aim to investigate this relationship by examining the subcellular localization of small RNA loading and viral replication in Arabidopsis. Our findings reveal that Argonaute 2 (AGO2), a key component of RNA silencing, loads small RNAs at the endoplasmic reticulum (ER)–chloroplast membrane contact sites (MCSs). We identify a chloroplast-localized protein, RNA helicase 3 (RH3), which interacts with AGO2 and facilitates the loading of small RNAs into AGO2 at these MCSs. Furthermore, we discover that MCSs serve as replication sites for certain plant viruses. RH3 also promotes the loading of viral-derived small RNAs into AGO2, thereby enhancing plant antiviral resistance. Overall, our study sheds light on the roles of RH3 in RNA silencing and plant antiviral defenses, providing valuable insights into the cytobiological connections between RNA silencing, viral replication, and antiviral immunity. This study reveals that RNA silencing component Argonaute 2 (AGO2) loads small RNAs at endoplasmic reticulum–chloroplast membrane contact sites with the help of RNA helicase 3 (RH3), which also enhances the loading of viral-derived small RNAs. These findings highlight the connections between RNA silencing, viral replication, and plant antiviral resistance.