mRNA ADENOSINE METHYLASE promotes drought tolerance through N6-methyladenosine-dependent and independent impacts on mRNA regulation in Arabidopsis.

Among many mRNA modifications, adenine methylation at the N⁶ position (N⁶-methyladenosine, m⁶A) is known to affect mRNA biology extensively. The influence of m⁶A has yet to be assessed under drought, one of the most impactful abiotic stresses. We show that Arabidopsis thaliana (L.) Heynh. (Arabidopsis) plants lacking mRNA ADENOSINE METHYLASE (MTA) are drought-sensitive. Subsequently, we comprehensively assess the impacts of MTA-dependent m⁶A changes during drought on mRNA abundance, stability, and translation in Arabidopsis. During drought, there is a global trend toward hypermethylation of many protein-coding transcripts that does not occur in mta. We also observe complex regulation of m⁶A at a transcript-specific level, possibly reflecting compensation by other m⁶A components. Importantly, a subset of transcripts that are hypermethylated in an MTA-dependent manner exhibited reduced turnover and translation in mta, compared with wild-type (WT) plants, during drought. Additionally, MTA impacts transcript stability and translation independently of m⁶A. We also correlate drought-associated deposition of m⁶A with increased translation of modulators of drought response, such as RD29A, COR47, COR413, ALDH2B, ERD7, and ABF4 in WT, which is impaired in mta. m⁶A is dynamic during drought and, alongside MTA, promotes tolerance by regulating drought-responsive changes in transcript turnover and translation.