m6Amodified

m6Amodified is a term used to refer to RNA molecules that carry the N6-methyladenosine (m6A) modification. m6A is the most prevalent internal modification in eukaryotic mRNA and many long noncoding RNAs, influencing transcript processing, localization, stability, translation, and overall gene expression. The modification is added by a writer complex that typically includes METTL3 as the catalytic subunit and METTL14 as an essential partner, along with regulatory factors such as WTAP, VIRMA, and ZC3H13. Demethylases such as FTO and ALKBH5 can remove m6A, making the modification dynamic. Reader proteins, including YTHDF1-3, YTHDC1, and IGF2BP family members, recognize m6A and mediate downstream effects on RNA metabolism.

Genomic distribution and sequence context: m6A sites are enriched around stop codons and in 3' untranslated regions, with active roles in alternative splicing and RNA export. The prevalent consensus motif associated with m6A is DRACH (D = A/G/U, R = A/G, H = A/C/U), though not all m6A sites conform strictly to this motif.

Detection and study: m6Amodified transcripts are identified and mapped using antibody-based enrichment methods such as MeRIP-seq or m6A-seq, along with crosslinking-based approaches (e.g., miCLIP) for higher-resolution mapping. Additional site-specific and quantitative methods exist to measure stoichiometry and functional impact.

Biological significance: m6Amodified RNAs contribute to development, cellular differentiation, and responses to stress by modulating splicing, translation efficiency, mRNA decay, and nuclear export. Dysregulation of m6A modification or its regulators has been linked to various diseases, including cancers and neurological disorders, making the study of m6Amodified transcripts an active area of functional genomics and biomedical research.