Systematic identification of edited microRNAs in the human brain.

Systematic identification of edited microRNAs in the human brain.
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DOI:
10.1101/gr.131573.111
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发表时间:
2012-08
期刊:
影响因子:
7
通讯作者:
Eisenberg E
Eisenberg E
中科院分区:
生物学1区
文献类型:
--
作者:
Alon S;Mor E;Vigneault F;Church GM;Locatelli F;Galeano F;Gallo A;Shomron N;Eisenberg E

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腺苷-肌苷(A-to-I)编辑修饰基因组蓝图中的RNA转录物。这一过程的先决条件是双链RNA (dsRNA)结构。这些dsrna是作为microRNA (miRNA)成熟过程的一部分形成的,因此预计miRNA会受到A-to-I编辑的影响。mirna的编辑有可能为基因调控途径增加另一层复杂性,特别是如果编辑发生在miRNA-mRNA识别位点。因此,研究这种现象的程度是很有意义的。目前的文献报道对其程度不一致;虽然一些报道声称它可能很普遍,但另一些报道认为报道的事件很罕见。利用下一代测序(NGS)方法,辅以广泛的生物信息学分析,我们能够系统地识别来自人类脑组织的成熟mirna中的a -to- i编辑事件。我们的算法成功地鉴定了成熟mirna中许多已知的编辑位点,并揭示了17个新的人类位点,其中12个位于mirna的识别位点。我们使用体外ADAR过表达试验证实了大多数编辑事件。大多数网站的编辑效率很低。在公开的小鼠脑区组织数据集中也得到了类似的结果。因此,我们发现A-to-I编辑确实改变了几种mirna,但并不普遍。
Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA–mRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread, others deem the reported events as rare. Utilizing a next-generation sequencing (NGS) approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread.
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