Deciphering the basis for m6A selectivity

N6-methyladenosine (m6A), a widespread destabilizing mark on mRNA, is non-uniformly distributed across the transcriptome, yet the basis for its selective deposition is unknown. Here, we propose that m6A deposition is not selective. Instead, it is exclusion-based: m6A consensus motifs are methylated by default, unless they are within a window of ~100 nt from a splice junction. A simple model which we extensively validate, relying exclusively on presence of m6A motifs and exon-intron architecture, allows recapitulation of experimentally-measured m6A profiles and the vast majority of m6A hallmarks, including a strong inverse correlation with mRNA stability. Our findings establish a mechanism coupling nuclear mRNA splicing and packaging with the covalent installation of m6A, which in turn controls cytoplasmic m6A-mediated decay.