miR6157 Targets ERD2a-Like and Negatively Regulates Tobacco Resistance Against Tobacco Mosaic Virus

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.