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Modulation of host gene expression by the zinc finger antiviral protein [CLIP-seq]

ABSTRACT: The zinc finger antiviral protein (ZAP) depletes non-self RNAs through recognition of their elevated CpG dinucleotide content. CpG dinucleotides are sparse in most endogenous mammalian mRNAs, but a subset might potentially be modulated by ZAP. While CpG frequency alone is insufficient to predict ZAP-regulation, we developed an algorithm using experimentally determined compositional features to predict which endogenous mRNAs may be ZAP-regulated. Using ZAP-knockout mice, we demonstrate that levels of many host mRNAs that are algorithmically predicted ZAP targets are indeed increased when ZAP is absent. ZAP is interferon-inducibel and we also identify genes that are downregulated by ZAP during an innate immune response. Many ZAP-regulated gene products are extracellular matrix or of nucleosome components, whose ZAP mediated control is conserved in human cells. Overall, we provide a new tool for the prediction of ZAP target genes and reveal host mRNAs that are ZAP-regulated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE274582 | GEO | 2024/09/01

REPOSITORIES: GEO

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Modulation of host gene expression by the zinc finger antiviral protein [RNA-seq]

Project description:The zinc finger antiviral protein (ZAP) depletes non-self RNAs through recognition of their elevated CpG dinucleotide content. CpG dinucleotides are sparse in most endogenous mammalian mRNAs, but a subset might potentially be modulated by ZAP. While CpG frequency alone is insufficient to predict ZAP-regulation, we developed an algorithm using experimentally determined compositional features to predict which endogenous mRNAs may be ZAP-regulated. Using ZAP-knockout mice, we demonstrate that levels of many host mRNAs that are algorithmically predicted ZAP targets are indeed increased when ZAP is absent. ZAP is interferon-inducibel and we also identify genes that are downregulated by ZAP during an innate immune response. Many ZAP-regulated gene products are extracellular matrix or of nucleosome components, whose ZAP mediated control is conserved in human cells. Overall, we provide a new tool for the prediction of ZAP target genes and reveal host mRNAs that are ZAP-regulated.

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