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

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

PROVIDER: PRJNA1147233 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30230600_1.fastq.gz	Fastqsanger.gz
	SRR30230600_2.fastq.gz	Fastqsanger.gz
	SRR30230601_1.fastq.gz	Fastqsanger.gz
	SRR30230601_2.fastq.gz	Fastqsanger.gz
	SRR30230602_1.fastq.gz	Fastqsanger.gz

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

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

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

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Project description:Synonymous recoding of viral genome can attenuate their replication, but can have pleiotropic effects, with multiple mechanisms contributing to attenuation. We set out to design recoded viral genomes whose attenuation was specific and conditional. The zinc finger antiviral protein (ZAP) recognizes CpG dinucleotides and targets CpG-rich RNAs for depletion, but RNA features such as CpG numbers, spacing and surrounding nucleotide composition that enable specific modulation by ZAP are undescribed. Using synonymously mutated HIV-1 genomes, we define several sequence features that govern ZAP sensitivity and stable attenuation. Using features defined using HIV-1, we then designed a mutant enterovirus A71 genome whose attenuation was also stable and strictly ZAP-dependent, both in cell culture and in mice. This conditionally attenuated enterovirus A71 elicited neutralizing antibodies that were protective against wild-type enterovirus 71 infection and disease. Elucidation of the determinants of ZAP sensitivity can thus enable the rational design of conditionally attenuated viral vaccines.

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