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Basic Characteristics of Mutations
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Mutation Site
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F17A |
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Mutation Site Sentence
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N protein with a F17A mutation fails to localise to deaminase-containing RNA granules and reduces host deaminase-dependent mutagenesis of SARS-CoV-2 genome. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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N |
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Standardized Encoding Gene
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N
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Genotype/Subtype
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- |
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Viral Reference
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NC_045512
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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39567830
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Title
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Viral N protein hijacks deaminase-containing RNA granules to enhance SARS-CoV-2 mutagenesis
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Author
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Li Z,Luo L,Ju X,Huang S,Lei L,Yu Y,Liu J,Zhang P,Chi T,Ma P,Huang C,Huang X,Ding Q,Zhang Y
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Journal
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The EMBO journal
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Journal Info
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2024 Dec;43(24):6444-6468
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Abstract
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Host cell-encoded deaminases act as antiviral restriction factors to impair viral replication and production through introducing mutations in the viral genome. We sought to understand whether deaminases are involved in SARS-CoV-2 mutation and replication, and how the viral factors interact with deaminases to trigger these processes. Here, we show that APOBEC and ADAR deaminases act as the driving forces for SARS-CoV-2 mutagenesis, thereby blocking viral infection and production. Mechanistically, SARS-CoV-2 nucleocapsid (N) protein, which is responsible for packaging viral genomic RNA, interacts with host deaminases and co-localizes with them at stress granules to facilitate viral RNA mutagenesis. N proteins from several coronaviruses interact with host deaminases at RNA granules in a manner dependent on its F17 residue, suggesting a conserved role in modulation of viral mutagenesis in other coronaviruses. Furthermore, mutant N protein bearing a F17A substitution cannot localize to deaminase-containing RNA granules and leads to reduced mutagenesis of viral RNA, providing support for its function in enhancing deaminase-dependent viral RNA editing. Our study thus provides further insight into virus-host cell interactions mediating SARS-CoV-2 evolution.
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Sequence Data
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-
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