Researchers from the Beijing Institute of Genomics of the Chinese Academy of Sciences have made a groundbreaking discovery regarding the mechanism behind the most common mammalian mRNA modification. This new study, led by Prof. Ren Jie and Prof. Yang Yungui, sheds light on the process of N6-methyladenosine (m6A) RNA modification, which has significant implications for gene expression and disease.

The study, published in Molecular Cell, unravels the intricate process of m6A modification, which affects the entire life cycle of mRNA, including pre-mRNA splicing, 3′-end processing, nuclear export, translation, stability, and decay. The modification is catalyzed by the methyltransferase complex (MTC) and is shaped by the inhibitory role of the exon junction complex, leading to a specific enrichment toward stop codons.

One of the key findings of the study is the establishment of the m6A modification pattern co-transcriptionally, before RNA synthesis is complete. The researchers also identified m6A on R-loops, which are three-stranded nucleic acid structures formed co-transcriptionally and play a vital role in regulating gene expression, DNA replication, and modification.

To investigate how m6A might be installed co-transcriptionally, the researchers performed a protein co-immunoprecipitation (co-IP) to identify the proteins associated with m6A methyltransferase. Their findings provide crucial insights into the mechanism underlying the m6A RNA modification, paving the way for further understanding of gene expression regulation and potential disease mechanisms.