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

Background: N6-methyladenosine (m6A), a prevalent mRNA modification, is dynamically regulated by methyltransferases, including METTL3 and METTL14. Materials & methods: In the current study, we employed a custom hybrid-seq method to identify novel METTL3 / 14 transcripts, explore their protein-coding capacities and predict the putative role of the METTL isoforms. Results: 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. Conclusion: Our findings offer significant insights into the intricate transcriptional landscape of METTL3 / 14 , shedding light on the regulatory mechanisms underlying methylation in mRNAs.