Transcriptome-wide analysis reveals spatial correlation between N6-methyladenosine and binding sites of microRNAs and RNA-binding proteins.

N6-methyladenosine (mA), the most prevalent epitranscriptomic modification in eukaryotes, is enriched in 3'-untranslated regions (3'UTRs) of mRNAs. As 3'UTRs are major binding sites of RNA-binding proteins (RBPs) and microRNAs (miRNAs), mA-dependent local RNA structure change may alter the accessibility of RBPs and miRNAs to their target sites and regulate mRNA function. Using a human transcriptome-wide computational analysis to investigate the relation between mA, RBPs and miRNAs, we find a strong positive correlation between number of mA sites, miRNAs and RBPs binding to mRNAs, suggesting mA-modified mRNAs are more targeted by miRNAs and RBPs. Moreover, mA sites are located proximally to miRNA target sites and binding sites of multiple RBPs. Further, miRNA target sites and RBP-binding sites located close to each other are also located proximally to mA. This study indicates three-way interplay between mA, microRNA and RBP binding, suggesting the influence of mRNA modifications on the miRNA and RBP interactomes.