Maturation of the Human Dorsolateral Prefrontal Cortex Coincides With a Dynamic Shift in MicroRNA Expression
Maturation of the Human Dorsolateral Prefrontal Cortex Coincides With a Dynamic Shift in MicroRNA Expression
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DOI：
10.1093/schbul/sbs198
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发表时间：
2014-03-01
影响因子：
6.6
通讯作者：
Cairns, Murray J.
中科院分区：
文献类型：
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作者：
Beveridge, Natalie J.;Santarelli, Danielle M.;Cairns, Murray J.
microRNA是一种小分子RNA，它为RNA诱导的沉默复合物提供特异性，这构成了转录后调控的精细组合系统的基础。这个系统对于复杂的后生动物来说是必不可少的，在大脑皮层的发育中得到了例证。为了详细探讨人类大脑皮层miRNA表达的复杂性，我们使用miRNA微阵列分析了97名2个月至78岁的受试者死后前额叶皮层的RNA。总体miRNA表达在青春期后显著下降之前的早年最高（n = 140下降，n = 32增加）。青春期后期也以上升轨迹上的miRNA与大多数下降之间的拐点为标志。在相同组织中显示反向mRNA表达模式的靶基因的功能注释在神经发育重要途径中过度表达，包括神经系统疾病（最显著的是精神分裂症），神经系统发育和细胞间信号传导。由于成熟的miRNA表达在很大程度上是转录后调节的，因此还检测了miRNA生物发生基因的表达。Dicer和Exportin-5显示出与年龄的显著相关性;然而，两者都与整个生命周期的总体miRNA表达无关。皮质miRNA表达的研究为理解发育和衰老过程中复杂的转录后调控环境提供了一个框架，这些环境可能形成神经发育障碍中观察到的变化的底物。
MicroRNA are small RNAs that provide specificity for the RNA induced silencing complex, which forms the basis of an exquisite combinatorial system for posttranscriptional regulation. This system, essential for complex metazoans, is exemplified in the development of the cerebral cortex. To explore the complexity of human cortical miRNA expression in detail, we analyzed RNA from postmortem prefrontal cortex from 97 subjects aged 2 months to 78 years using miRNA microarray. Global miRNA expression was highest in the early years before declining significantly after adolescence (n = 140 decreased, n = 32 increased). Late adolescence was also marked by an inflection point between miRNA on an upward trajectory vs the majority going down. Functional annotation of target genes displaying inverse mRNA expression patterns in the same tissue were over-represented in neurodevelopmentally significant pathways including neurological disease (most significantly schizophrenia), nervous system development, and cell-to-cell signaling. As mature miRNA expression is largely posttranscriptionally regulated, miRNA biogenesis gene expression was also examined. Dicer and Exportin-5 displayed significant associations with age; however, neither correlated with global miRNA expression across the lifespan. This investigation of cortical miRNA expression provides a framework for understanding the complex posttranscriptional regulatory environment during development and aging that may form a substrate for changes observed in neurodevelopmental disorders.