miR-142-5p Disrupts Neuronal Morphogenesis Underlying Porcine Hemagglutinating Encephalomyelitis Virus Infection by Targeting Ulk1

Li, Zi; Lan, Yungang; Zhao, Kui; Lv, Xiaoling; Ding, Ning; Lu, Huijun; Zhang, Jing; Yue, Huiqing; Shi, Junchao; Song, Deguang; Gao, Feng; He, Wenqi

How might miR-142-5p molecules exert their functions? We performed deep sequencing and bioinformatics analyses, demonstrating that miR-142-5p could target the Ulk1 mRNA 3 ′ UTR in vitro and in vivo. To gain insight into the function of the target gene, RNAi-mediated knockdown and adenovirus mediated overexpression of Ulk1 was performed, and we found that Ulk1 are required for axonal elongation and dendritic spines formation. This observation was consistent with a previous study that demonstrated that Unc51.1/Ulk1 was required for granule cell axon and dendrite spines formation (Tomoda et al., 1999 (Tomoda et al., , 2004 . Generally, in the mammalian forebrain, the majority of excitatory synapses are located on dendritic spines, and the size of the spines correlates well with the strength of synaptic transmission (Paulin et al., 2016) . Abnormal structural plasticity of excitatory synapses has also been strongly implicated in many neurodevelopmental, psychiatric, and neurodegenerative disorders (Woolfrey and Srivastava, 2016) . Furthermore, co-localization of miR-142-5p and Ulk1 along axon shafts and/or within growth cones supported the functional involvement of these structures in modulating the neuron morphogenesis response to PHE. Consequently, we concluded that the abundance of miR-142-5p could repress Ulk1 mRNA, resulting in limited synthesis of new Ulk1 protein and restricted neuronal morphogenesis in underlying PHEV infection.