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

ABSTRACT: Protein homeostasis (proteostasis) is in part maintained by co-translational quality control mechanisms that prevent errors during protein synthesis by targeting aberrant polypeptides for degradation. While such systems are relatively well-characterized in yeast and animals, their identity and regulation in plants remain poorly understood, and broader knowledge of how organisms synchronise protein production with quality control is lacking. In eukaryotes, the Target of Rapamycin (TOR) kinase drives translation, but a direct link to co-translational surveillance has not been established. Here, we identify three NOT4-like E3 ubiquitin ligases (NOT4A-C) as TOR-regulated factors that coordinate co-translational protein quality control to limit proteotoxic stress in Arabidopsis thaliana. Loss of NOT4 function increases TOR activity and global translation rates, and leads to an accumulation of polyubiquitylated proteins, as well as hypersensitivity to proteasome and TOR inhibition and protein misfolding stress. We found that NOT4A co-localizes with TOR in cytoplasmic foci, and not4 mutants phenocopy TOR-inhibited wild-type plants for a subset of transcriptional and growth-related outputs, indicating that NOT4s are downstream of and essential for normal TOR signalling. Furthermore, we found that elevated translation in NOT4-deficient plants provides enhanced resistance to Pseudomonas syringae pv. Tomato, suggesting a functional interplay between translational quality control and defence against pathogens that suppress host translation. Our study uncovers a previously uncharacterised TOR–NOT4 signalling axis that may act to proportionately couple translational throughput with quality control capacity to safeguard the plant proteome under both optimal and challenged conditions. Since TOR and NOT4-like proteins are conserved in plants, animals, and fungi, we suggest this mechanism may operate more broadly across eukaryotic taxa.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE319908 | GEO | 2026/08/11

REPOSITORIES: GEO