# Arabidopsis thaliana iron superoxide dismutase FeSOD1 protects ARGONAUTE 1 in a copper-dependent manner

## TL;DR

This study shows that the protein FeSOD1 protects AGO1 in plants under copper deficiency, helping maintain gene silencing.

## Contribution

The study identifies FeSOD1 as a novel copper-dependent regulator of AGO1 stability in plants.

## Key findings

- FeSOD1 interacts with AGO1 and is enriched under copper deficiency.
- fsd1-2 mutants have reduced AGO1 levels and increased target mRNA accumulation.
- FeSOD1 protects AGO1 from oxidative stress-induced degradation.

## Abstract

Copper (Cu) deficiency compromises plant growth and limits crop productivity. Plants respond to Cu scarcity by activating the expression of several miRNAs, known as Cu-miRNAs, which degrade mRNAs from various cuproproteins to conserve Cu. Cu-miRNAs, like most plant miRNAs, associate with ARGONAUTE 1 (AGO1), the primary effector protein of miRNA-mediated gene silencing pathways, whose function is typically modulated by interacting proteins acting as cofactors. However, how AGO1 is regulated and functions under Cu deficiency remains unknown. Here, we searched for AGO1 interactors in Arabidopsis thaliana plants expressing a functional AGO1 protein tagged with the Twin-Strep-tag (TST) polypeptide, grown under Cu-sufficient or Cu-deficient conditions. TST–AGO1 complexes were affinity purified, and proteins were identified using tandem MS. Interestingly, the iron superoxide dismutase 1 (FeSOD1) encoded by FSD1 was enriched in TST–AGO1 complexes purified from plants grown under Cu deficiency. Moreover, fsd1-2 mutant plants showed reduced levels of AGO1 compared with wild-type plants under Cu sufficiency, while both Cu-miRNA-specific and general AGO1 target mRNAs accumulated to higher levels in fsd1-2 plants under both Cu-deficient and Cu-sufficient conditions compared with wild-type plants. These findings suggest that FeSOD1 is essential for proper AGO1 function, and that its superoxide dismutase activity, which mitigates oxidative stress, enhances AGO1 stability, particularly under Cu deficiency.

AGO1 is essential for Cu-deficiency responses but is sensitive to oxidative stress. FeSOD1 interacts with AGO1 and protects it from superoxide radical-induced degradation, thereby preserving miRNA-mediated gene silencing pathways.

Graphical Abstract