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人类大脑显示出反复出现的非经典微小RNA编辑事件,这些事件在种子序列中富集,可能具有功能后果。

Human Brain Shows Recurrent Non-Canonical MicroRNA Editing Events Enriched for Seed Sequence with Possible Functional Consequence.

作者信息

Paul Deepanjan, Ansari Asgar Hussain, Lal Megha, Mukhopadhyay Arijit

机构信息

CSIR-Institute of Genomics & Integrative Biology, Delhi 110025, India.

Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh 201002, India.

出版信息

Noncoding RNA. 2020 Jun 2;6(2):21. doi: 10.3390/ncrna6020021.

DOI:10.3390/ncrna6020021
PMID:32498345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7345632/
Abstract

RNA editing is a post-transcriptional modification, which can provide tissue-specific functions not encoded in DNA. Adenosine-to-inosine is the predominant editing event and, along with cytosine-to-uracil changes, constitutes canonical editing. The rest is non-canonical editing. In this study, we have analysed non-canonical editing of microRNAs in the human brain. We have performed massively parallel small RNA sequencing of frontal cortex (FC) and corpus callosum (CC) pairs from nine normal individuals (post-mortem). We found 113 and 90 unique non-canonical editing events in FC and CC samples, respectively. More than 70% of events were in the miRNA seed sequence-implicating an altered set of target mRNAs and possibly resulting in a functional consequence. Up to 15% of these events were recurring and found in at least three samples, also supporting the biological relevance of such variations. Two specific sequence variations, C-to-A and G-to-U, accounted for over 80% of non-canonical miRNA editing events-and revealed preferred sequence motifs. Our study is one of the first reporting non-canonical editing in miRNAs in the human brain. Our results implicate miRNA non-canonical editing as one of the contributing factors towards transcriptomic diversity in the human brain.

摘要

RNA编辑是一种转录后修饰,它能够提供DNA中未编码的组织特异性功能。腺苷到肌苷是主要的编辑事件,并且与胞嘧啶到尿嘧啶的变化一起构成了典型编辑。其余的则是非典型编辑。在本研究中,我们分析了人类大脑中微小RNA的非典型编辑。我们对来自9名正常个体(尸检)的额叶皮质(FC)和胼胝体(CC)样本进行了大规模平行小RNA测序。我们分别在FC和CC样本中发现了113个和90个独特的非典型编辑事件。超过70%的事件发生在微小RNA种子序列中,这意味着一组靶mRNA发生了改变,并可能导致功能后果。其中高达15%的事件是重复性的,且在至少三个样本中被发现,这也支持了此类变异的生物学相关性。两种特定的序列变异,即C到A和G到U,占非典型微小RNA编辑事件的80%以上,并揭示了偏好的序列基序。我们的研究是首批报道人类大脑中微小RNA非典型编辑的研究之一。我们的结果表明,微小RNA非典型编辑是导致人类大脑转录组多样性的因素之一。

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