m6A landscape in human tissue

RNA N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in eukaryotes. It has emerged as a critical post-transcriptional regulatory mechanism of gene expression, affecting various biological processes, such as stress response, immunity, development, and oncogenesis. To elucidate the global distribution and regulation of m6A RNA methylation and establish a m6A co-methylation network, we performed m6A sequencing and profiled the m6A landscape of 66 different human tissues using RNA pools obtained from multiple donors. This comprehensive dataset revealed the prevalence of m6A sites in human transcripts, some shared across a broad range of tissues and some with tissue-restricted modification patterns. We found m6A sites to be evolutionarily constrained between species and within human populations, thus indicating the functional significance of m6A methylation. By analyzing the m6A co-methylation network across human tissues, in conjunction with investigating the binding footprints of RNA binding proteins in the vicinity of m6A sites, we established evidence that the RNA binding protein FXR2 may function as a negative regulator of m6A modified transcripts in neuronal tissues. Collectively, our study provides a comprehensive resource for m6A RNA methylation in human tissues and sheds light on the functional significance and tissue-specific regulation of this modification.