# Disruption of the mRNA m6A writer complex triggers autoimmunity in Arabidopsis

## TL;DR

Disrupting the mRNA m6A writer complex in Arabidopsis causes autoimmunity, with defense genes activated and temperature affecting the response.

## Contribution

This study reveals autoimmunity as a major consequence of mRNA m6A writer complex disruption in plants.

## Key findings

- Disruption of the mRNA m6A writer complex in Arabidopsis triggers autoimmunity and defense gene activation.
- Autoimmune responses in m6A writer complex mutants are temperature-sensitive, with stronger effects at 17°C.
- Changes in mRNA poly(A) tail length correlate with autoimmune phenotypes in these mutants.

## Abstract

Distinguishing self from non-self is crucial to direct immune responses against pathogens. Unmodified RNAs stimulate human innate immunity, but RNA modifications suppress this response. mRNA m6A modification is essential for Arabidopsis thaliana viability. However, the molecular basis of the impact of mRNA m6A depletion is poorly understood. Here, we show that disruption of the Arabidopsis mRNA m6A writer complex triggers autoimmunity. Most gene expression changes in m6A writer complex vir-1 mutants grown at 17°C are explained by defence gene activation and are suppressed at 27°C, consistent with the frequent temperature sensitivity of Arabidopsis immunity. Accordingly, we found enhanced pathogen resistance and increased premature cell death in vir-1 mutants at 17°C but not 27°C. Global temperature-sensitive mRNA poly(A) tail length changes accompany these phenotypes. Our results demonstrate that autoimmunity is a major phenotype of mRNA m6A writer complex mutants, with important implications for interpreting the role of this modification. Furthermore, we open the broader question of whether unmodified RNA triggers immune signalling in plants.

Genes are transcribed into RNA, and some RNAs are chemically modified in ways that ultimately influence gene function. The most frequently occurring modification of messenger RNA is methylation of adenosine at the N6 position (denoted as m6A). The role of m6A is context and species-specific. Mutation of components of the mRNA m6A writer complex in the model plant Arabidopsis thaliana results in embryo lethality. However, what makes mRNA m6A modification essential in Arabidopsis is currently unknown. In this study, we asked what changes in gene expression occurred in viable Arabidopsis mutants that had significantly reduced mRNA m6A levels. We found that the most prominent changes in gene expression fell into the categories of defence or immune response. Defence gene expression patterns are frequently temperature sensitive in Arabidopsis. Remarkably, we found that 91% of the genes upregulated in mRNA m6A mutants at 17 °C were not upregulated at 27 °C. Therefore, the main finding of this study is that mRNA m6A mutants exhibit autoimmunity. This raises the question of how defence signalling is activated in mRNA m6A mutants. Furthermore, to understand the direct role of mRNA m6A, approaches that consider the widespread indirect changes in autoimmune gene expression will be required.