Genomics ( IF 4.4 ) Pub Date : 2020-12-16 , DOI: 10.1016/j.ygeno.2020.12.027 Sukhen Das Mandal 1 , Partho Sarothi Ray 1
N6-methyladenosine (m6A), the most prevalent epitranscriptomic modification in eukaryotes, is enriched in 3′-untranslated regions (3′UTRs) of mRNAs. As 3′UTRs are major binding sites of RNA-binding proteins (RBPs) and microRNAs (miRNAs), m6A-dependent local RNA structure change may alter the accessibility of RBPs and miRNAs to their target sites and regulate mRNA function. Using a human transcriptome-wide computational analysis to investigate the relation between m6A, RBPs and miRNAs, we find a strong positive correlation between number of m6A sites, miRNAs and RBPs binding to mRNAs, suggesting m6A-modified mRNAs are more targeted by miRNAs and RBPs. Moreover, m6A sites are located proximally to miRNA target sites and binding sites of multiple RBPs. Further, miRNA target sites and RBP-binding sites located close to each other are also located proximally to m6A. This study indicates three-way interplay between m6A, microRNA and RBP binding, suggesting the influence of mRNA modifications on the miRNA and RBP interactomes.
中文翻译:
全转录组分析揭示了 N6-甲基腺苷与 microRNA 和 RNA 结合蛋白的结合位点之间的空间相关性
N6-甲基腺苷 (m 6 A) 是真核生物中最普遍的表观转录组修饰,富含 mRNA 的 3'-非翻译区 (3'UTR)。由于 3'UTR 是 RNA 结合蛋白 (RBP) 和 microRNA (miRNA) 的主要结合位点,m 6 A 依赖性局部 RNA 结构变化可能会改变 RBP 和 miRNA 对其靶位点的可及性并调节 mRNA 功能。使用人类转录组范围的计算分析来研究 m 6 A、RBP 和 miRNA 之间的关系,我们发现 m 6 A 位点的数量、miRNA 和与 mRNA 结合的 RBP 之间存在强正相关,这表明 m 6 A 修饰的 mRNA 是miRNA 和 RBP 更有针对性。此外,m 6A 位点位于 miRNA 靶位点和多个 RBP 的结合位点附近。此外,彼此靠近的 miRNA 靶位点和 RBP 结合位点也位于 m 6 A 的近端。该研究表明 m 6 A、microRNA 和 RBP 结合之间的三向相互作用,表明 mRNA 修饰对 miRNA 的影响和 RBP 相互作用组。