Jiao Bolei, Wu Baijun, Liu Sucen, Han Hongyan, Fang Haonan, Xi Dehui
Key Laboratory of Bio-Resource and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
Southwest Bio-Resources R&D Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan, China.
Physiol Plant. 2025 Sep-Oct;177(5):e70590. doi: 10.1111/ppl.70590.
Plants employ intricate molecular mechanisms to combat viral infections. MicroRNAs (miRNAs) play critical roles in regulating gene expression, influencing plant growth, development, and immunity. Endoplasmic Reticulum (ER) luminal protein receptor 2 (ERD2) positively regulates immunity to several human diseases and serves as a potential target for the development of new therapeutic strategies. However, the role of miRNAs and ERD2 in plant response to virus infection remains largely unknown. Here, we demonstrate that miR6157 negatively modulates tobacco resistance against tobacco mosaic virus (TMV) by targeting the ERD2a-like gene (ERD2aL). Overexpression of miR6157 in Nicotiana tabacum significantly enhanced TMV accumulation, while silencing of miR6157 increased tobacco antiviral defense. MiR6157 could suppress the expression of ERD2aL, thereby attenuating the unfolded protein response (UPR) pathway. Conversely, overexpression of ERD2aL activated UPR-related genes (bZIP60, CRT1, Bip) and conferred resistance to TMV in both N. tabacum and Nicotiana benthamiana. TMV infection dynamically upregulated the expression of ERD2aL and UPR-related marker genes. Tunicamycin (TM) or dithiothreitol (DTT) treatment activated ERD2aL expression and the UPR pathway, and reduced virus accumulation. Importantly, exogenous TM treatment rescued the antiviral capacity in miR6157-overexpressing plants or ERD2aL-silenced plants, underscoring the central role of the UPR pathway in ERD2aL-mediated immunity. This study reveals that the miR6157/ERD2aL module works as a key regulator of UPR signaling in plant antiviral defense, offering insights for engineering antiviral transgenic crops.
植物利用复杂的分子机制来对抗病毒感染。微小RNA（miRNA）在调节基因表达、影响植物生长、发育和免疫方面发挥着关键作用。内质网（ER）腔蛋白受体2（ERD2）对几种人类疾病的免疫起正向调节作用，并可作为开发新治疗策略的潜在靶点。然而，miRNA和ERD2在植物对病毒感染的反应中的作用在很大程度上仍不清楚。在这里，我们证明miR6157通过靶向类ERD2a基因（ERD2aL）负向调节烟草对烟草花叶病毒（TMV）的抗性。在烟草中过表达miR6157显著增强了TMV的积累，而沉默miR6157则增强了烟草的抗病毒防御。miR6157可以抑制ERD2aL的表达，从而减弱未折叠蛋白反应（UPR）途径。相反，过表达ERD2aL激活了UPR相关基因（bZIP60、CRT1、Bip），并使烟草和本氏烟草对TMV产生抗性。TMV感染动态上调了ERD2aL和UPR相关标记基因的表达。衣霉素（TM）或二硫苏糖醇（DTT）处理激活了ERD2aL的表达和UPR途径，并减少了病毒积累。重要的是，外源TM处理挽救了过表达miR6157的植物或沉默ERD2aL的植物的抗病毒能力，强调了UPR途径在ERD2aL介导的免疫中的核心作用。这项研究表明，miR6157/ERD2aL模块在植物抗病毒防御中作为UPR信号的关键调节因子发挥作用，为工程化抗病毒转基因作物提供了见解。
