Department of Animal and Poultry Science, College of Aburaihan, University of Tehran, Tehran, Iran.
Division of Animal Sciences, University of Missouri, Columbia, MO, United States of America.
PLoS One. 2018 Feb 22;13(2):e0193316. doi: 10.1371/journal.pone.0193316. eCollection 2018.
RNA editing increases the diversity of the transcriptome and proteome. Adenosine-to-inosine (A-to-I) editing is the predominant type of RNA editing in mammals and it is catalyzed by the adenosine deaminases acting on RNA (ADARs) family. Here, we used a largescale computational analysis of transcriptomic data from brain, heart, colon, lung, spleen, kidney, testes, skeletal muscle and liver, from three adult animals in order to identify RNA editing sites in bovine. We developed a computational pipeline and used a rigorous strategy to identify novel editing sites from RNA-Seq data in the absence of corresponding DNA sequence information. Our methods take into account sequencing errors, mapping bias, as well as biological replication to reduce the probability of obtaining a false-positive result. We conducted a detailed characterization of sequence and structural features related to novel candidate sites and found 1,600 novel canonical A-to-I editing sites in the nine bovine tissues analyzed. Results show that these sites 1) occur frequently in clusters and short interspersed nuclear elements (SINE) repeats, 2) have a preference for guanines depletion/enrichment in the flanking 5'/3' nucleotide, 3) occur less often in coding sequences than other regions of the genome, and 4) have low evolutionary conservation. Further, we found that a positive correlation exists between expression of ADAR family members and tissue-specific RNA editing. Most of the genes with predicted A-to-I editing in each tissue were significantly enriched in biological terms relevant to the function of the corresponding tissue. Lastly, the results highlight the importance of the RNA editome in nervous system regulation. The present study extends the list of RNA editing sites in bovine and provides pipelines that may be used to investigate the editome in other organisms.
RNA 编辑增加了转录组和蛋白质组的多样性。腺苷到肌苷（A-to-I）编辑是哺乳动物中主要的 RNA 编辑类型，它由腺苷脱氨酶作用于 RNA（ADAR）家族催化。在这里，我们使用大规模的计算分析了来自大脑、心脏、结肠、肺、脾、肾、睾丸、骨骼肌和肝脏的三种成年动物的转录组数据，以鉴定牛的 RNA 编辑位点。我们开发了一种计算管道，并使用严格的策略从缺乏相应 DNA 序列信息的 RNA-Seq 数据中识别新的编辑位点。我们的方法考虑了测序错误、映射偏差以及生物学复制，以降低获得假阳性结果的概率。我们对与新候选位点相关的序列和结构特征进行了详细的描述，并在分析的 9 种牛组织中发现了 1600 个新的规范 A-to-I 编辑位点。结果表明，这些位点 1）经常出现在簇和短散在核元件（SINE）重复中，2）在侧翼 5'/3'核苷酸中偏爱鸟嘌呤耗竭/富集，3）在编码序列中比基因组的其他区域发生得更少，4）进化保守性低。此外，我们发现 ADAR 家族成员的表达与组织特异性 RNA 编辑之间存在正相关。每个组织中预测具有 A-to-I 编辑的大多数基因在与相应组织功能相关的生物学术语中显著富集。最后，结果强调了 RNA 编辑组在神经系统调节中的重要性。本研究扩展了牛的 RNA 编辑位点列表，并提供了可用于研究其他生物体编辑组的管道。
