Ayana R, Singh Shailja, Pati Soumya
1 Department of Life Sciences, School of Natural Sciences, Shiv Nadar University , Greater Noida, Uttar Pradesh, India .
2 Special Center for Molecular Medicine, Jawaharlal Nehru University , Delhi, India .
Stem Cells Dev. 2017 Apr 15;26(8):541-553. doi: 10.1089/scd.2016.0290. Epub 2017 Mar 6.
Unraveling transcriptional heterogeneity and the labyrinthine nature of neurodevelopment can probe insights into neuropsychiatric disorders. It is noteworthy that adult neurogenesis is restricted to the subventricular and subgranular zones of the brain. Recent studies suggest long non-coding RNAs (lncRNAs) as an avant-garde class of regulators implicated in neurodevelopment. But, paucity exists in the knowledge regarding lncRNAs in neurogenesis and their associations with neurodevelopmental defects. To address this, we extensively reviewed the existing literature databases as well as performed relevant in-silico analysis. We utilized Allen Brain Atlas (ABA) differential search module and generated a catalogue of ∼30,000 transcripts specific to the neurogenic zones, including coding and non-coding transcripts. To explore the existing lncRNAs reported in neurogenesis, we performed extensive literature mining and identified 392 lncRNAs. These degenerate lncRNAs were mapped onto the ABA transcript list leading to detection of 20 lncRNAs specific to neurogenic zones (Dentate gyrus/Lateral ventricle), among which 10 showed associations to several neurodevelopmental disorders following in-silico mapping onto brain disease databases like Simons Foundation Autism Research Initiative, AutDB, and lncRNADisease. Notably, using ABA correlation module, we could establish lncRNA-to-mRNA coexpression networks for the above 10 candidate lncRNAs. Finally, pathway prediction revealed physical, biochemical, or regulatory interactions for nine lncRNAs. In addition, ABA differential search also revealed 54 novel significant lncRNAs from the null set (∼30,000). Conclusively, this review represents an updated catalogue of lncRNAs in neurogenesis and neurological diseases, and overviews the field of OMICs-based data analysis for understanding lncRNome-based regulation in neurodevelopment.
揭示转录异质性和神经发育的迷宫般本质有助于深入了解神经精神疾病。值得注意的是，成体神经发生仅限于大脑的室下区和颗粒下区。最近的研究表明，长链非编码RNA（lncRNA）作为一类前沿的调节因子参与神经发育。但是，关于lncRNA在神经发生中的作用及其与神经发育缺陷的关联，我们所知甚少。为了解决这个问题，我们广泛查阅了现有文献数据库，并进行了相关的计算机模拟分析。我们利用艾伦脑图谱（ABA）差异搜索模块，生成了一个约30000个特定于神经发生区域的转录本目录，包括编码和非编码转录本。为了探索神经发生中报道的现有lncRNA，我们进行了广泛的文献挖掘，鉴定出392个lncRNA。这些退化的lncRNA被映射到ABA转录本列表上，从而检测到20个特定于神经发生区域（齿状回/侧脑室）的lncRNA，其中10个在计算机模拟映射到如西蒙斯基金会自闭症研究倡议、AutDB和lncRNADisease等脑部疾病数据库后，显示与几种神经发育障碍有关。值得注意的是，使用ABA相关模块，我们可以为上述10个候选lncRNA建立lncRNA与mRNA的共表达网络。最后，通路预测揭示了9个lncRNA的物理、生化或调节相互作用。此外，ABA差异搜索还从空集（约30000个）中发现了54个新的重要lncRNA。总之，本综述代表了神经发生和神经疾病中lncRNA的更新目录，并概述了基于组学的数据分析领域，以了解神经发育中基于lncRNA组的调控。
