m⁶A modulates RNA structure

N⁶-methyladenosine (m⁶A) is an RNA modification that regulates transcript metabolism. Liu et al. now report that m⁶A induces structural remodelling in RNAs and that this affects gene expression. They found that a m⁶A in a hairpin at the human MALAT1 non-coding RNA enhanced interactions with the RNA-binding protein hnRNP-C, by promoting a structural switch ('m⁶A switch') in the hairpin that made the proximal hnRNP-C binding motif single-stranded and accessible. Transcriptome-wide analyses identified multiple m⁶A residues proximal to hnRNP-C-bound sites, and RNA structure mapping of m⁶A–hnRNP-C binding sites supported the global occurrence of m⁶A switching. Moreover, the expression of >800 m⁶A-switch-containing genes was affected similarly by knocking down HNRNPC or m⁶A methylases, resulting in lower proliferation and aberrant splicing in the vicinity of m⁶A switches. Thus, m⁶A-mediated RNA structural remodelling alters RNA–protein interactions and gene expression.