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转录组范围分析揭示 N6-甲基腺苷与 microRNAs 和 RNA 结合蛋白结合位点之间的空间相关性。

Transcriptome-wide analysis reveals spatial correlation between N6-methyladenosine and binding sites of microRNAs and RNA-binding proteins.

机构信息

Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur, Nadia, 741246, West Bengal, India.

Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur, Nadia, 741246, West Bengal, India.

出版信息

Genomics. 2021 Jan;113(1 Pt 1):205-216. doi: 10.1016/j.ygeno.2020.12.027. Epub 2020 Dec 16.

DOI:10.1016/j.ygeno.2020.12.027
PMID:33340693
Abstract

N6-methyladenosine (mA), 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), mA-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 mA, RBPs and miRNAs, we find a strong positive correlation between number of mA sites, miRNAs and RBPs binding to mRNAs, suggesting mA-modified mRNAs are more targeted by miRNAs and RBPs. Moreover, mA 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 mA. This study indicates three-way interplay between mA, microRNA and RBP binding, suggesting the influence of mRNA modifications on the miRNA and RBP interactomes.

摘要

N6-甲基腺苷(mA)是真核生物中最普遍的转录后修饰,在 mRNA 的 3'非翻译区(3'UTR)中富集。由于 3'UTR 是 RNA 结合蛋白(RBPs)和 microRNA(miRNAs)的主要结合位点,mA 依赖性局部 RNA 结构变化可能改变 RBPs 和 miRNAs 与靶位点的可及性,并调节 mRNA 功能。我们使用人类转录组范围的计算分析来研究 mA、RBPs 和 miRNAs 之间的关系,发现 mA 位点的数量、与 mRNAs 结合的 miRNAs 和 RBPs 之间存在很强的正相关,这表明 mA 修饰的 mRNAs 更容易被 miRNAs 和 RBPs 靶向。此外,mA 位点靠近 miRNA 靶位点和多个 RBPs 的结合位点。此外,彼此靠近的 miRNA 靶位点和 RBP 结合位点也靠近 mA。这项研究表明 mA、microRNA 和 RBP 结合之间的三向相互作用,表明 mRNA 修饰对 miRNA 和 RBP 相互作用组的影响。

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