New insights into the dynamics of m6A epitranscriptome: hybrid-seq identifies novel mRNAs of the m6A writers METTL3/14

<b>Background:</b> N6-methyladenosine (m6A), a prevalent mRNA modification, is dynamically regulated by methyltransferases, including METTL3 and METTL14.<b>Materials & methods:</b> In the current study, we employed a custom hybrid-seq method to identify novel <i>METTL3</i>/<i>14</i> transcripts, explore their protein-coding capacities and predict the putative role of the METTL isoforms.<b>Results:</b> Demultiplexing of the hybrid-seq barcoded datasets unraveled the expression patterns of the newly identified mRNAs in major malignancies as well as in non-malignant cells, providing a deeper understanding of the methylation pathways. Open reading frame query revealed novel METTL3/14 isoforms, broadening our perspective for the structural diversity within METTL family.<b>Conclusion:</b> Our findings offer significant insights into the intricate transcriptional landscape of <i>METTL3</i>/<i>14</i>, shedding light on the regulatory mechanisms underlying methylation in mRNAs.