N6-Adenosine Methylation in MiRNAs

Methylation of N6-adenosine (m6A) has been observed in many different classes of RNA, but its prevalence in microRNAs (miRNAs) has not yet been studied. Here we show that a knockdown of the m6A demethylase FTO affects the steady-state levels of several miRNAs. Moreover, RNA immunoprecipitation with an anti-m6A-antibody followed by RNA-seq revealed that a significant fraction of miRNAs contains m6A. By motif searches we have discovered consensus sequences discriminating between methylated and unmethylated miRNAs. The epigenetic modification of an epigenetic modifier as described here adds a new layer to the complexity of the posttranscriptional regulation of gene expression.N6-甲基腺苷（m6A）修饰已在多种RNA类别中被报道，但其在微小RNA（miRNAs）中的修饰发生率尚未得到研究。本研究证实，对m6A去甲基化酶FTO进行基因敲低，会改变多种微小RNA的稳态水平。此外，采用抗m6A抗体进行RNA免疫沉淀后结合RNA测序（RNA-seq）的实验分析表明，相当比例的微小RNA携带m6A修饰。通过基序搜索，我们鉴定出了可区分甲基化与非甲基化微小RNA的共有序列。本文所揭示的表观遗传调控因子的表观遗传修饰，为基因表达转录后调控的复杂性新增了一个调控维度。