Kunxin Wu, Yan Fu, Pingjuan Zhao, Qiuxian Xie, Shuxia Li, Yadan Wu, Xueting Liu, Ping Gan, Mengbin Ruan, Xiuchun Zhang
The evolutionary arms race between plants and viruses hinges on the sophistication of host defense mechanisms and viral counter-defenses. RNA silencing serves as a fundamental antiviral strategy in plants, primarily mediated by Dicer-like (DCL) proteins such as DCL4, which is stabilized by its canonical cofactor double-stranded RNA-binding protein 4 (DRB4). Interestingly, residual DCL4 activity persists in drb4 mutants, suggesting the existence of compensatory pathways. Here, we identify DRB7.1 and DRB7.2, each of which contains a single double-stranded RNA-binding motif, as essential cofactors that sustain DCL4-dependent antiviral defense in the absence of DRB4. This functional compensation occurs despite a lack of sequence homology with DRB4, illustrating a novel mechanism of "structural substitution" whereby functional redundancy is achieved through divergent domain architecture rather than sequence conservation. Furthermore, we show that Turnip crinkle virus actively subverts this backup defense through its coat protein, which directly interacts with both DRB7.1 and DRB7.2 and promotes their degradation via the ubiquitin-proteasome system. Our findings reveal a multi-layered molecular arms race centered on cofactor homeostasis, highlighting how plants use structural plasticity to maintain antiviral silencing and how viruses dynamically adapt by hijacking the host degradation system. This study redefines conventional notions of functional redundancy in antiviral defense and highlights the intricate coevolution between RNA silencing components and viral counter-defense strategies.