Motti Dario, Lerch Jessica K, Danzi Matt C, Gans Jared H, Kuo Frank, Slepak Tatiana I, Bixby John L, Lemmon Vance P
The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, FL, USA.
Department of Neuroscience, Ohio State University, Columbus, OH, USA.
FEBS Lett. 2017 Jul;591(14):2091-2105. doi: 10.1002/1873-3468.12718. Epub 2017 Jul 2.
Peripheral neurons regenerate their axons after injury. Transcriptional regulation by microRNAs (miRNAs) is one possible mechanism controlling regeneration. We profiled miRNA expression in mouse dorsal root ganglion neurons after a sciatic nerve crush, and identified 49 differentially expressed miRNAs. We evaluated the functional role of each miRNA using a phenotypic analysis approach. To predict the targets of the miRNAs we employed RNA-Sequencing and examined transcription at the isoform level. We identify thousands of differentially expressed isoforms and bioinformatically associate the miRNAs that modulate neurite growth with their putative target isoforms to outline a network of regulatory events underlying peripheral nerve regeneration. MiR-298, let-7a, and let-7f enhance neurite growth and target the majority of isoforms in the differentially expressed network.
外周神经元在损伤后会再生其轴突。微小RNA（miRNA）的转录调控是控制再生的一种可能机制。我们对坐骨神经挤压后小鼠背根神经节神经元中的miRNA表达进行了分析，并鉴定出49种差异表达的miRNA。我们使用表型分析方法评估了每种miRNA的功能作用。为了预测miRNA的靶标，我们采用了RNA测序并在异构体水平上检查转录情况。我们鉴定出数千种差异表达的异构体，并通过生物信息学方法将调节神经突生长的miRNA与其推定的靶标异构体相关联，以勾勒出外周神经再生潜在的调控事件网络。MiR-298、let-7a和let-7f可促进神经突生长，并靶向差异表达网络中的大多数异构体。
