N6-Methyladenosine mRNA methylation is important for salt stress tolerance in Arabidopsis

As the most abundant internal modification of mRNA, N-6-methyladenosine (m(6)A) methylation of RNA is emerging as a new layer of epitranscriptomic gene regulation in cellular processes, including embryo development, flowering-time control, microspore generation and fruit ripening, in plants. However, the cellular role of m(6)A in plant responses to environmental stimuli remains largely unexplored. In this study, we show that m(6)A methylation plays an important role in salt stress tolerance in Arabidopsis. All mutants of m(6)A writer components, including MTA, MTB, VIRILIZER (VIR) and HAKAI, displayed salt-sensitive phenotypes in an m(6)A-dependent manner. The vir mutant, in which the level of m(6)A was most highly reduced, exhibited salt-hypersensitive phenotypes. Analysis of the m(6)A methylome in the vir mutant revealed a transcriptome-wide loss of m(6)A modification in the 3MODIFIER LETTER PRIME untranslated region (3MODIFIER LETTER PRIME-UTR). We demonstrated further that VIR-mediated m(6)A methylation modulates reactive oxygen species homeostasis by negatively regulating the mRNA stability of several salt stress negative regulators, including ATAF1, GI and GSTU17, through affecting 3MODIFIER LETTER PRIME-UTR lengthening linked to alternative polyadenylation. Our results highlight the important role played by epitranscriptomic mRNA methylation in the salt stress response of Arabidopsis and indicate a strong link between m(6)A methylation and 3MODIFIER LETTER PRIME-UTR length and mRNA stability during stress adaptation.