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SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs
Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200321/ https://www.ncbi.nlm.nih.gov/pubmed/35658050 http://dx.doi.org/10.1371/journal.ppat.1010599 |
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author | Cao, Lili Luo, Yujie Guo, Xuefei Liu, Shengde Li, Siji Li, Junhong Zhang, Zeming Zhao, Yingchi Zhang, Qiao Gao, Feng Ji, Xiong Gao, Xiang Li, Yunfei You, Fuping |
author_facet | Cao, Lili Luo, Yujie Guo, Xuefei Liu, Shengde Li, Siji Li, Junhong Zhang, Zeming Zhao, Yingchi Zhang, Qiao Gao, Feng Ji, Xiong Gao, Xiang Li, Yunfei You, Fuping |
author_sort | Cao, Lili |
collection | PubMed |
description | Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses. |
format | Online Article Text |
id | pubmed-9200321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92003212022-06-16 SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs Cao, Lili Luo, Yujie Guo, Xuefei Liu, Shengde Li, Siji Li, Junhong Zhang, Zeming Zhao, Yingchi Zhang, Qiao Gao, Feng Ji, Xiong Gao, Xiang Li, Yunfei You, Fuping PLoS Pathog Research Article Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses. Public Library of Science 2022-06-03 /pmc/articles/PMC9200321/ /pubmed/35658050 http://dx.doi.org/10.1371/journal.ppat.1010599 Text en © 2022 Cao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Cao, Lili Luo, Yujie Guo, Xuefei Liu, Shengde Li, Siji Li, Junhong Zhang, Zeming Zhao, Yingchi Zhang, Qiao Gao, Feng Ji, Xiong Gao, Xiang Li, Yunfei You, Fuping SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs |
title | SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs |
title_full | SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs |
title_fullStr | SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs |
title_full_unstemmed | SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs |
title_short | SAFA facilitates chromatin opening of immune genes through interacting with anti-viral host RNAs |
title_sort | safa facilitates chromatin opening of immune genes through interacting with anti-viral host rnas |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200321/ https://www.ncbi.nlm.nih.gov/pubmed/35658050 http://dx.doi.org/10.1371/journal.ppat.1010599 |
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