Virus Genes

, Volume 54, Issue 3, pp 343–350 | Cite as

HSV-1-encoded microRNA miR-H1 targets Ubr1 to promote accumulation of neurodegeneration-associated protein

  • Kai ZhengEmail author
  • Qiuying Liu
  • Shaoxiang Wang
  • Zhe Ren
  • Kaio Kitazato
  • Depo YangEmail author
  • Yifei WangEmail author


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.


HSV-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).

Author contributions

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Supplementary material

11262_2018_1551_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouChina
  2. 2.School of Pharmaceutical Sciences, School of MedicineShenzhen UniversityShenzhenChina
  3. 3.School of Life Science and Technology, Guangzhou Jinan Biomedicine Research and Development CenterJinan UniversityGuangzhouChina
  4. 4.Division of Molecular Pharmacology of Infectious Agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

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