Exon-intron boundary inhibits m6A deposition, enabling m6A distribution hallmark, longer mRNA half-life and flexible protein coding

• Published in: Nature communications Vol. 14; no. 1; p. 4172
• Main Authors: Luo, Zhiyuan, Ma, Qilian, Sun, Shan, Li, Ningning, Wang, Hongfeng, Ying, Zheng, Ke, Shengdong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.07.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114/1305; 631/337/1645/2570; 631/45/500; Deep learning; Deposition; Enhancers; Exons; Genomes; Heterogeneity; Humanities and Social Sciences; mRNA; mRNA stability; multidisciplinary; N6-methyladenosine; Proteins; RNA modification; Science; Science (multidisciplinary); Splice junctions
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39897-1

Regional bias of N 6 -methyladenosine (m 6 A) mRNA modification avoiding splice site region, calls for an open hypothesis whether exon-intron boundary could affect m 6 A deposition. By deep learning modeling, we find that exon-intron boundary represses a proportion (12% to 34%) of m 6 A deposition at adjacent exons (~100 nt to splice site). Experiments validate that m 6 A signal increases once the host gene does not undergo pre-mRNA splicing to produce the same mRNA. Inhibited m 6 A sites have higher m 6 A enhancers and lower m 6 A silencers locally and show high heterogeneity at different exons genome-widely, with only a small proportion (12% to 15%) of exons showing strong inhibition, enabling more stable mRNAs and flexible protein coding. m 6 A is majorly responsible for why mRNAs with more exons be more stable. Exon junction complex (EJC) only partially contributes to this exon-intron boundary m 6 A inhibition in some short internal exons, highlighting additional factors yet to be identified. m 6 A mRNA modification is not typically found near splice junctions in mRNAs. Here the authors show exon-intron boundary inhibits m6A deposition at ~100 nt region nearby splice site, enabling m 6 A distribution hallmark, more stable mRNA and flexible protein coding.