HSV-1-encoded microRNA miR-H1 targets Ubr1 to promote accumulation of neurodegeneration-associated protein
Herpes simplex virus 1 (HSV-1) encodes various microRNAs (miRNAs), whose targets are largely unknown. miR-H1 is the first discovered HSV-1 miRNA and is expressed predominantly in productive infection. Here we show that ubiquitin protein ligase E3 component n-recognin 1 (Ubr1) is a cellular target of miR-H1. Ubr1 is a RING-type E3 ubiquitin ligase of the Arg/N-end rule pathway, which causes the degradation of proteins bearing “destabilizing” N-terminal residues, such as neurodegeneration-associated protein fragment β-amyloid. Using model substrates, we found that miR-H1 significantly repressed the expression and activity of Ubr1. Consequently, miR-H1-mediated Ubr1 silencing resulted in the accumulation of β-amyloid, which might contribute to the neurodegenerative pathogenesis enhanced by HSV-1. Our results provide novel insights into the mechanism by which HSV-1-encoded miR-H1 functions in neurodegenerative pathogenesis through targeting Ubr1-mediated Arg/N-end rule degradation pathway.
KeywordsHSV-1 miRNA Ubr1 Neurodegeneration Ubiquitin
We thank Dr. Xiao Wang for her kindly support. This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81603341, 81573471, and 81274170), the China Postdoctoral Science Foundation (Grant Nos. 2015M570726 and 2015M582472), and the Shenzhen Science and Technology Project (No. JCYJ20150324141711568).
KZ, DY, and YW designed the research. KZ, QL, SW, ZR, and KK helped with the experiments, data analysis, and discussion. KZ and YW wrote the manuscript.
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Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors. Therefore, informed content was not required for this work.