The study investigates the role of N6-methyladenosine (m6A) in regulating RNA-protein interactions, particularly with heterogeneous nuclear ribonucleoprotein C (hnRNP C). m6A is a common internal modification in eukaryotic messenger RNA (mRNA) and long non-coding RNA (lncRNA), but its physiological significance remains unclear. The authors demonstrate that m6A controls the accessibility of RNA-binding motifs (RBM) within RNA structures, a mechanism they term "m6A-switch." This mechanism affects RNA-protein interactions, influencing gene expression and RNA maturation. Using PAR-CLIP and m6A/Mek RIP approaches, the researchers identified 39,060 m6A-switches among hnRNP C binding sites. Global reduction of m6A decreased hnRNP C binding at 2,798 high-confidence m6A-switches. These m6A-switch-regulated hnRNP C binding activities affect both mRNA abundance and alternative splicing. The study provides insights into how RNA-binding proteins gain regulated access to their RBMs through m6A-dependent RNA structural remodeling, highlighting the widespread impact of m6A on cellular biology.The study investigates the role of N6-methyladenosine (m6A) in regulating RNA-protein interactions, particularly with heterogeneous nuclear ribonucleoprotein C (hnRNP C). m6A is a common internal modification in eukaryotic messenger RNA (mRNA) and long non-coding RNA (lncRNA), but its physiological significance remains unclear. The authors demonstrate that m6A controls the accessibility of RNA-binding motifs (RBM) within RNA structures, a mechanism they term "m6A-switch." This mechanism affects RNA-protein interactions, influencing gene expression and RNA maturation. Using PAR-CLIP and m6A/Mek RIP approaches, the researchers identified 39,060 m6A-switches among hnRNP C binding sites. Global reduction of m6A decreased hnRNP C binding at 2,798 high-confidence m6A-switches. These m6A-switch-regulated hnRNP C binding activities affect both mRNA abundance and alternative splicing. The study provides insights into how RNA-binding proteins gain regulated access to their RBMs through m6A-dependent RNA structural remodeling, highlighting the widespread impact of m6A on cellular biology.