A biochemical landscape of A-to-I RNA editing in the human brain transcriptome.
A biochemical landscape of A-to-I RNA editing in the human brain transcriptome.
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DOI：
10.1101/gr.162537.113
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发表时间：
2014-03
期刊：
影响因子：
7
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Sakurai M;Ueda H;Yano T;Okada S;Terajima H;Mitsuyama T;Toyoda A;Fujiyama A;Kawabata H;Suzuki T
肌苷是人类转录组中的一种丰富的RNA修饰，在转录后水平调节基因表达的许多生物学过程中都是必不可少的。作用于RNA的腺苷脱氨酶(ADARs)在双链区催化腺苷的水解性脱氨为肌苷(A-to-I编辑)。我们之前建立了一种名为肌苷化学擦除(ICE)的生化方法，以高可靠性直接鉴定RNA链上的肌苷。在这里，我们应用ICE结合深度测序的方法(ICE-seq)对人类成年大脑转录组中的A-to-I编辑位点进行了无偏见的全基因组筛选。与传统ICE方法确定的位点相结合，我们绘制了19791个新位点，新发现了1258个编辑后的mRNAs，其中66个新位点位于编码区，其中41个导致氨基酸分配改变。ICE-SEQ在各种重复元件和短发夹中发现了新的编辑位点。基因本体论分析表明，这些编辑后的mRNAs与转录、能量代谢和神经疾病相关，为人类大脑功能的各个方面提供了新的见解。
Inosine is an abundant RNA modification in the human transcriptome and is essential for many biological processes in modulating gene expression at the post-transcriptional level. Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosines to inosines (A-to-I editing) in double-stranded regions. We previously established a biochemical method called “inosine chemical erasing” (ICE) to directly identify inosines on RNA strands with high reliability. Here, we have applied the ICE method combined with deep sequencing (ICE-seq) to conduct an unbiased genome-wide screening of A-to-I editing sites in the transcriptome of human adult brain. Taken together with the sites identified by the conventional ICE method, we mapped 19,791 novel sites and newly found 1258 edited mRNAs, including 66 novel sites in coding regions, 41 of which cause altered amino acid assignment. ICE-seq detected novel editing sites in various repeat elements as well as in short hairpins. Gene ontology analysis revealed that these edited mRNAs are associated with transcription, energy metabolism, and neurological disorders, providing new insights into various aspects of human brain functions.
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