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- Title
HSV-1-encoded microRNA miR-H1 targets Ubr1 to promote accumulation of neurodegeneration-associated protein.
- Authors
Zheng, Kai; Liu, Qiuying; Wang, Shaoxiang; Ren, Zhe; Kitazato, Kaio; Yang, Depo; Wang, Yifei
- Abstract
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.
- Subjects
MICRORNA; NEURODEGENERATION; UBIQUITIN; GENE expression; PROTEINS
- Publication
Virus Genes, 2018, Vol 54, Issue 3, p343
- ISSN
0920-8569
- Publication type
Article
- DOI
10.1007/s11262-018-1551-6