TOR-NOT4 signalling couples translation to co-translational quality control in plants.

Protein synthesis must be tightly coordinated with quality control to prevent proteotoxic stress, yet the mechanisms underlying co-translational surveillance in plants, and how these are aligned with translational output, remain poorly understood. Here, we identify three NOT4-like E3 ubiquitin ligases in Arabidopsis thaliana as regulators of co-translational protein quality control and uncover a functional link between NOT4 and TARGET OF RAPAMYCIN (TOR) signalling that coordinates quality-control capacity with translational output. Loss of NOT4 function increases basal TOR activity and global translation rates, resulting in the accumulation of polyubiquitylated proteins and heightened sensitivity to proteasome inhibition, TOR inhibition, and protein misfolding stress. Consistent with prior evidence that NOT4 proteins are TOR-regulated phosphotargets, not4 mutants also phenocopy TOR-inhibited wild-type plants for a subset of transcriptional and growth-related processes. Furthermore, elevated translation in NOT4-deficient plants enhances resistance to Pseudomonas syringae pv. tomato. Collectively, our findings reveal a functional coupling between TOR signalling and NOT4 activity that may scale quality control with translational demand to safeguard proteome homoeostasis across eukaryotes.