Bisulphite miRNA-seq reveals widespread CpG and non-CpG 5-(hydroxy)methyl-Cytosine in human microRNAs

Bisulphite miRNA-seq reveals widespread CpG and non-CpG 5-(hydroxy)methyl-Cytosine in human microRNAs
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DOI:
10.1080/15476286.2021.1927423
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发表时间:
2021-06-06
期刊:
影响因子:
4.1
通讯作者:
Fulci, Valerio
Fulci, Valerio
中科院分区:
生物学3区
文献类型:
--
作者:
Carissimi, Claudia;Laudadio, Ilaria;Fulci, Valerio

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在过去的十年中,epitranscriptomics领域强调了广泛的人类RNA,包括microRNA(miRNA)的转录后修饰。最近的研究表明,人类miRNAs发生胞嘧啶甲基化。我们描述了第一个基于NGS的高通量方法(BS-miRNA-seq)和分析管道(MAmBA),以获得人类miRNA中(羟基)-甲基-5-胞嘧啶((h)m5 C)修饰的高分辨率映射。我们的方法揭示了miRNAs在不同的序列背景下都经历了广泛的胞嘧啶修饰。此外,我们的数据与特异性抗体的验证揭示了人类成熟miRNAs中的m5 C和hm 5C残基。BS-miRNA-seq和MAmBA可能有助于在各种细胞类型和组织中精确定位(h)m5 C在miRNA上的位置,这是理解这种修饰在miRNA中的功能意义的关键成就。MAmBA可在https://github.com/flcvlr/MAmBA下载
In the last decade, the field of epitranscriptomics highlighted a wide array of post-transcriptional modifications in human RNAs, including microRNAs (miRNAs). Recent reports showed that human miRNAs undergo cytosine methylation. We describe the first high-throughput NGS-based method (BS-miRNA-seq) and an analysis pipeline (MAmBA) to attain high-resolution mapping of (hydroxy)-methyl-5-cytosine ((h)m5C) modifications in human miRNAs. Our method uncovers that miRNAs undergo widespread cytosine modification in various sequence contexts.Furthermore, validation of our data with specific antibodies reveals both m5C and hm5C residues in human mature miRNAs. BS-miRNA-seq and MAmBA may contribute to the precise mapping of (h)m5C on miRNAs in various cell types and tissues, a key achievement towards the understanding of the functional implications of this modification in miRNAs. MAmBA is available for download at https://github.com/flcvlr/MAmBA