Cross-talk between m6A and m1A regulators, YTHDF2 and ALKBH3 fine-tunes mRNA expression

The recently re-discovered interest in N6-methyl adenosine (m6A) - one of more than a hundred modifications found on eukaryotic mRNA (known as epi-transcriptomic codes) - is currently one of the most topical areas in science. The m6A methylation impacts on all aspects of cellular RNA metabolism and several physiological processes. Although less abundant than the m6A epitranscriptomic mark, the m1A methylation has recently also attracted interest due to its dynamic nature in response to physiological changes. We investigated the role of the YTH domain-containing m6A reader protein family and the m1A eraser ALKBH3 on the expression of a transgene in mammalian cells. We present the first evidence that expression of a transgene is subjected to co-ordinated regulation by both m6A and m1A regulators. In addition, we provide genetic data implicating that the m6A reader YTHDF2 can read m1A site. Furthermore, we show that the m1A eraser ALKBH3 is a target of m1A methylation.