RNA methylomes reveal the m(6)A-mediated regulation of DNA demethylase gene SlDML2 in tomato fruit ripening

BACKGROUND: Methylation of nucleotides, notably in the forms of 5-methylcytosine (5mC) in DNA and N(6)-methyladenosine (m(6)A) in mRNA, carries important information for gene regulation. 5mC has been elucidated to participate in the regulation of fruit ripening, whereas the function of m(6)A in this process and the interplay between 5mC and m(6)A remain uncharacterized. RESULTS: Here, we show that mRNA m(6)A methylation exhibits dynamic changes similar to DNA methylation during tomato fruit ripening. RNA methylome analysis reveals that m(6)A methylation is a prevalent modification in the mRNA of tomato fruit, and the m(6)A sites are enriched around the stop codons and within the 3′ untranslated regions. In the fruit of the ripening-deficient epimutant Colorless non-ripening (Cnr) which harbors DNA hypermethylation, over 1100 transcripts display increased m(6)A levels, while only 134 transcripts show decreased m(6)A enrichment, suggesting a global increase in m(6)A. The m(6)A deposition is generally negatively correlated with transcript abundance. Further analysis demonstrates that the overall increase in m(6)A methylation in Cnr mutant fruit is associated with the decreased expression of RNA demethylase gene SlALKBH2, which is regulated by DNA methylation. Interestingly, SlALKBH2 has the ability to bind the transcript of SlDML2, a DNA demethylase gene required for tomato fruit ripening, and modulates its stability via m(6)A demethylation. Mutation of SlALKBH2 decreases the abundance of SlDML2 mRNA and delays fruit ripening. CONCLUSIONS: Our study identifies a novel layer of gene regulation for key ripening genes and establishes an essential molecular link between DNA methylation and mRNA m(6)A methylation during fruit ripening. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13059-019-1771-7) contains supplementary material, which is available to authorized users.