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

Author:
Lu, Liangsheng, Zhang, Fan, Li, Yuting, Yang, AnYong, Guan, Chenguang, Ding, Xin, Liu, Yuan, Liu, Yuyan, Zhang, Chen-Yu, Li, Liang, Zhang, Qipeng
Source:
Biochemical and biophysical research communications 2019 v.509 no.2 pp. 402-406
ISSN:
0006-291X
Subject:
Tick-borne encephalitis virus, cytotoxicity, gene expression, genes, messenger RNA, neurites, neuroplasticity, plasmid vectors, plasmids, proteins, virion
Abstract:
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.
Agid:
6280569