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

Virus Genes. 2018 Jun;54(3):343-350. doi: 10.1007/s11262-018-1551-6. Epub 2018 Mar 14.


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.

Keywords: HSV-1; Neurodegeneration; Ubiquitin; Ubr1; miRNA.

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • HEK293 Cells
  • Herpesvirus 1, Human / physiology*
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / physiology*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteolysis
  • RNA, Viral / biosynthesis
  • RNA, Viral / physiology*
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / metabolism*


  • Amyloid beta-Peptides
  • MicroRNAs
  • RNA, Viral
  • Ubiquitin
  • UBR1 protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex