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A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation
by
Sui, Baokun
, Wu, Qiong
, Fu, Zhen F.
, Lv, Lei
, Chen, Dong
, Li, Yingying
, Liu, Wei
, Huang, Fei
, Chen, Huanchun
, Zhao, Ling
, Li, Ruiming
, Zhou, Ming
, Zhang, Yi
, Hou, Jing
, Tian, Bin
, Jiang, Hao
, Xie, Juan
, Luo, Zhaochen
, Liu, Shiyong
, Cui, Min
, Tian, Yuling
, Zhang, Chengguang
in
Animal Genetics and Genomics
/ Animals
/ Antiviral drugs
/ Bioinformatics
/ Biomedical and Life Sciences
/ brain
/ Central nervous system
/ Central Nervous System Infections - metabolism
/ Central Nervous System Infections - virology
/ Chlorocebus aethiops
/ Cytoplasm
/ Degradation
/ Encephalitis
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Epigenetics
/ Evolutionary Biology
/ Experiments
/ EZH2, lncRNA, neurotropic virus, O-GlcNAcylation, PCP4L1
/ Female
/ Gene expression
/ genome
/ Genomes
/ Herpes simplex
/ Herpes viruses
/ Histone methyltransferase
/ histones
/ Host-Pathogen Interactions
/ Human alphaherpesvirus 1
/ Human Genetics
/ Indoles
/ Infections
/ Interferon
/ Kinases
/ Life Sciences
/ Lysosomes
/ Lysosomes - metabolism
/ Lyssavirus
/ methyltransferases
/ mice
/ Mice, Inbred C57BL
/ Microbial Genetics and Genomics
/ Nerve Tissue Proteins - metabolism
/ neurons
/ O-GlcNAcylation
/ peptides
/ Phosphorylation
/ Plant Genetics and Genomics
/ Proteins
/ Pyridones
/ Rabies
/ Rabies - metabolism
/ Rabies lyssavirus
/ Rabies virus - pathogenicity
/ Replication
/ RNA, Long Noncoding - metabolism
/ Semliki Forest virus
/ Stomatitis
/ Transcription
/ Vero Cells
/ Vesiculovirus
/ Viral infections
/ Virus Diseases - metabolism
/ Virus Replication
/ Viruses
2020
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A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation
by
Sui, Baokun
, Wu, Qiong
, Fu, Zhen F.
, Lv, Lei
, Chen, Dong
, Li, Yingying
, Liu, Wei
, Huang, Fei
, Chen, Huanchun
, Zhao, Ling
, Li, Ruiming
, Zhou, Ming
, Zhang, Yi
, Hou, Jing
, Tian, Bin
, Jiang, Hao
, Xie, Juan
, Luo, Zhaochen
, Liu, Shiyong
, Cui, Min
, Tian, Yuling
, Zhang, Chengguang
in
Animal Genetics and Genomics
/ Animals
/ Antiviral drugs
/ Bioinformatics
/ Biomedical and Life Sciences
/ brain
/ Central nervous system
/ Central Nervous System Infections - metabolism
/ Central Nervous System Infections - virology
/ Chlorocebus aethiops
/ Cytoplasm
/ Degradation
/ Encephalitis
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Epigenetics
/ Evolutionary Biology
/ Experiments
/ EZH2, lncRNA, neurotropic virus, O-GlcNAcylation, PCP4L1
/ Female
/ Gene expression
/ genome
/ Genomes
/ Herpes simplex
/ Herpes viruses
/ Histone methyltransferase
/ histones
/ Host-Pathogen Interactions
/ Human alphaherpesvirus 1
/ Human Genetics
/ Indoles
/ Infections
/ Interferon
/ Kinases
/ Life Sciences
/ Lysosomes
/ Lysosomes - metabolism
/ Lyssavirus
/ methyltransferases
/ mice
/ Mice, Inbred C57BL
/ Microbial Genetics and Genomics
/ Nerve Tissue Proteins - metabolism
/ neurons
/ O-GlcNAcylation
/ peptides
/ Phosphorylation
/ Plant Genetics and Genomics
/ Proteins
/ Pyridones
/ Rabies
/ Rabies - metabolism
/ Rabies lyssavirus
/ Rabies virus - pathogenicity
/ Replication
/ RNA, Long Noncoding - metabolism
/ Semliki Forest virus
/ Stomatitis
/ Transcription
/ Vero Cells
/ Vesiculovirus
/ Viral infections
/ Virus Diseases - metabolism
/ Virus Replication
/ Viruses
2020
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A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation
by
Sui, Baokun
, Wu, Qiong
, Fu, Zhen F.
, Lv, Lei
, Chen, Dong
, Li, Yingying
, Liu, Wei
, Huang, Fei
, Chen, Huanchun
, Zhao, Ling
, Li, Ruiming
, Zhou, Ming
, Zhang, Yi
, Hou, Jing
, Tian, Bin
, Jiang, Hao
, Xie, Juan
, Luo, Zhaochen
, Liu, Shiyong
, Cui, Min
, Tian, Yuling
, Zhang, Chengguang
in
Animal Genetics and Genomics
/ Animals
/ Antiviral drugs
/ Bioinformatics
/ Biomedical and Life Sciences
/ brain
/ Central nervous system
/ Central Nervous System Infections - metabolism
/ Central Nervous System Infections - virology
/ Chlorocebus aethiops
/ Cytoplasm
/ Degradation
/ Encephalitis
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Epigenetics
/ Evolutionary Biology
/ Experiments
/ EZH2, lncRNA, neurotropic virus, O-GlcNAcylation, PCP4L1
/ Female
/ Gene expression
/ genome
/ Genomes
/ Herpes simplex
/ Herpes viruses
/ Histone methyltransferase
/ histones
/ Host-Pathogen Interactions
/ Human alphaherpesvirus 1
/ Human Genetics
/ Indoles
/ Infections
/ Interferon
/ Kinases
/ Life Sciences
/ Lysosomes
/ Lysosomes - metabolism
/ Lyssavirus
/ methyltransferases
/ mice
/ Mice, Inbred C57BL
/ Microbial Genetics and Genomics
/ Nerve Tissue Proteins - metabolism
/ neurons
/ O-GlcNAcylation
/ peptides
/ Phosphorylation
/ Plant Genetics and Genomics
/ Proteins
/ Pyridones
/ Rabies
/ Rabies - metabolism
/ Rabies lyssavirus
/ Rabies virus - pathogenicity
/ Replication
/ RNA, Long Noncoding - metabolism
/ Semliki Forest virus
/ Stomatitis
/ Transcription
/ Vero Cells
/ Vesiculovirus
/ Viral infections
/ Virus Diseases - metabolism
/ Virus Replication
/ Viruses
2020
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A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation
Journal Article
A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation
2020
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Overview
Background
The central nervous system (CNS) is vulnerable to viral infection, yet few host factors in the CNS are known to defend against invasion by neurotropic viruses. Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in a wide variety of biological processes and are highly abundant in the mammalian brain, but their roles in defending against invasion of pathogens into the CNS remain unclear.
Results
We report here that multiple neurotropic viruses, including rabies virus, vesicular stomatitis virus, Semliki Forest virus, and herpes simplex virus 1, elicit the neuronal expression of a host-encoded lncRNA EDAL. EDAL inhibits the replication of these neurotropic viruses in neuronal cells and rabies virus infection in mouse brains. EDAL binds to the conserved histone methyltransferase enhancer of zest homolog 2 (EZH2) and specifically causes EZH2 degradation via lysosomes, reducing the cellular H3K27me3 level. The antiviral function of EDAL resides in a 56-nt antiviral substructure through which its 18-nt helix-loop intimately contacts multiple EZH2 sites surrounding T309, a known
O
-GlcNAcylation site. EDAL positively regulates the transcription of Pcp4l1 encoding a 10-kDa peptide, which inhibits the replication of multiple neurotropic viruses.
Conclusions
Our findings show that a neuronal lncRNA can exert an effective antiviral function via blocking a specific
O
-GlcNAcylation that determines EZH2 lysosomal degradation, rather than the traditional interferon-dependent pathway.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Animals
/ Biomedical and Life Sciences
/ brain
/ Central Nervous System Infections - metabolism
/ Central Nervous System Infections - virology
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ EZH2, lncRNA, neurotropic virus, O-GlcNAcylation, PCP4L1
/ Female
/ genome
/ Genomes
/ histones
/ Indoles
/ Kinases
/ mice
/ Microbial Genetics and Genomics
/ Nerve Tissue Proteins - metabolism
/ neurons
/ peptides
/ Proteins
/ Rabies
/ Rabies virus - pathogenicity
/ RNA, Long Noncoding - metabolism
/ Viruses
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