Institute of Neuroscience and State Key Laboratory of Neuroscience, Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
BMC Genomics. 2012 Jun 12;13:232. doi: 10.1186/1471-2164-13-232.
The morphogenesis of the cerebral cortex depends on the precise control of gene expression during development. Small non-coding RNAs, including microRNAs and other groups of small RNAs, play profound roles in various physiological and pathological processes via their regulation of gene expression. A systematic analysis of the expression profile of small non-coding RNAs in developing cortical tissues is important for clarifying the gene regulation networks mediating key developmental events during cortical morphogenesis.
Global profiling of the small RNA transcriptome was carried out in rat cerebral cortex from E10 till P28 using next-generation sequencing technique. We found an extraordinary degree of developmental stage-specific expression of a large group of microRNAs. A group of novel microRNAs with functional hints were identified, and brain-enriched expression and Dicer-dependent production of high-abundant novel microRNAs were validated. Profound editing of known microRNAs at "seed" sequence and flanking sequence was observed, with much higher editing events detected at late postnatal stages than embryonic stages, suggesting the necessity of microRNA editing for the fine tuning of gene expression during the formation of complicated synaptic connections at postnatal stages.
Our analysis reveals extensive regulation of microRNAs during cortical development. The dataset described here will be a valuable resource for clarifying new regulatory mechanisms for cortical development and diseases and will greatly contribute to our understanding of the divergence, modification, and function of microRNAs.
大脑皮层的形态发生依赖于发育过程中基因表达的精确控制。小非编码 RNA,包括 microRNAs 和其他小 RNA 组,通过调节基因表达在各种生理和病理过程中发挥着深远的作用。对皮质组织发育过程中小非编码 RNA 表达谱的系统分析,对于阐明介导皮质形态发生过程中关键发育事件的基因调控网络非常重要。
使用下一代测序技术,我们对 E10 至 P28 大鼠大脑皮层的小 RNA 转录组进行了全局分析。我们发现了一大组 microRNAs 具有非凡的发育阶段特异性表达程度。鉴定出一组具有功能暗示的新型 microRNAs,并验证了其在大脑中的丰富表达和 Dicer 依赖性产生。在“种子”序列和侧翼序列中观察到已知 microRNAs 的深刻编辑,在出生后阶段检测到的编辑事件比胚胎阶段多得多,这表明在出生后复杂的突触连接形成过程中,microRNA 编辑对于精细调节基因表达是必要的。
我们的分析揭示了 microRNAs 在皮质发育过程中的广泛调控。这里描述的数据集将是阐明皮质发育和疾病新调控机制的宝贵资源,并将极大地促进我们对 microRNAs 的分化、修饰和功能的理解。