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Dendritic targeted mRNA expression via a cis-acting RNA UTR element

Lu, Liangsheng, Zhang, Fan, Li, Yuting, Yang, AnYong, Guan, Chenguang, Ding, Xin, Liu, Yuan, Liu, Yuyan, Zhang, Chen-Yu, Li, Liang, Zhang, Qipeng
Biochemical and biophysical research communications 2019 v.509 no.2 pp. 402-406
Tick-borne encephalitis virus, cytotoxicity, gene expression, genes, messenger RNA, neurites, neuroplasticity, plasmid vectors, plasmids, proteins, virion
Local translation in neurites is considered as an important mechanism to modulate synaptic plasticity of neurons. However, it is hard to specifically express a protein-coding gene in neurites. Recently, the 5′-UTR of Tick-borne encephalitis virus (TBEV) is reported to be able to drive its RNA to the dendrites of infected neurons, as a cis-acting RNA element. To construct a neurite specific gene expression system, present study tested the ability of 5′-UTR of TBEV to bring a mRNA (mCherry CDS) to the neurites for targeted expression. We showed that both the 5′-UTR of TBEV and the 3′-UTR of Actb gene could bring the protein coding mRNA to neurites, and the TBEV 5′-UTR bearing mRNA was more robust targeted into neurites. About the safety of the TBEV 5′-UTR, there was no obvious cytotoxicity to the neurons when adding either cis-acting RNA element to the protein-expressing plasmid vectors. Given the short length and high efficiency of the TBEV 5′-UTR, the 5′-UTR of TBEV were assemble into an AAV plasmid to produce virus particles for expressing protein-coding gene in vivo. After two weeks infection, the TBEV 5′-UTR infected neurons expressed more mCherry protein in their neurites. In conclusion, as a short while high efficient cis-acting RNA element, TBEV 5′-UTR could be useful in neural system research and locally express synaptic proteins more precisely.