外显子
信使核糖核酸
无意义介导的衰变
生物
核糖核酸
基因
内含子
细胞生物学
甲基化
RNA剪接
分子生物学
遗传学
作者
P Cody He,Jiangbo Wei,Xiaoyang Dou,Bryan T. Harada,Zijie Zhang,Ruiqi Ge,Chang Liu,Li-Sheng Zhang,Xianbin Yu,Shuai Wang,Ruitu Lyu,Zhongyu Zou,Meng-Jie Chen,Chuan He
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2023-02-17
卷期号:379 (6633): 677-682
被引量:47
标识
DOI:10.1126/science.abj9090
摘要
N6-methyladenosine (m6A) is the most abundant messenger RNA (mRNA) modification and plays crucial roles in diverse physiological processes. Using a massively parallel assay for m6A (MPm6A), we discover that m6A specificity is globally regulated by suppressors that prevent m6A deposition in unmethylated transcriptome regions. We identify exon junction complexes (EJCs) as m6A suppressors that protect exon junction-proximal RNA within coding sequences from methylation and regulate mRNA stability through m6A suppression. EJC suppression of m6A underlies multiple global characteristics of mRNA m6A specificity, with the local range of EJC protection sufficient to suppress m6A deposition in average-length internal exons but not in long internal and terminal exons. EJC-suppressed methylation sites colocalize with EJC-suppressed splice sites, which suggests that exon architecture broadly determines local mRNA accessibility to regulatory complexes.
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