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DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis
Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations disrupting nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodefici...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836962/ https://www.ncbi.nlm.nih.gov/pubmed/27019227 http://dx.doi.org/10.1038/ni.3409 |
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author | Starokadomskyy, Petro Gemelli, Terry Rios, Jonathan J. Xing, Chao Wang, Richard C. Li, Haiying Pokatayev, Vladislav Dozmorov, Igor Khan, Shaheen Miyata, Naoteru Fraile, Guadalupe Raj, Prithvi Xu, Zhe Xu, Zigang Ma, Lin Lin, Zhimiao Wang, Huijun Yang, Yong Ben-Amitai, Dan Orenstein, Naama Mussaffi, Huda Baselga, Eulalia Tadini, Gianluca Grunebaum, Eyal Sarajlija, Adrijan Krzewski, Konrad Wakeland, Edward K. Yan, Nan de la Morena, Maria Teresa Zinn, Andrew R. Burstein, Ezra |
author_facet | Starokadomskyy, Petro Gemelli, Terry Rios, Jonathan J. Xing, Chao Wang, Richard C. Li, Haiying Pokatayev, Vladislav Dozmorov, Igor Khan, Shaheen Miyata, Naoteru Fraile, Guadalupe Raj, Prithvi Xu, Zhe Xu, Zigang Ma, Lin Lin, Zhimiao Wang, Huijun Yang, Yong Ben-Amitai, Dan Orenstein, Naama Mussaffi, Huda Baselga, Eulalia Tadini, Gianluca Grunebaum, Eyal Sarajlija, Adrijan Krzewski, Konrad Wakeland, Edward K. Yan, Nan de la Morena, Maria Teresa Zinn, Andrew R. Burstein, Ezra |
author_sort | Starokadomskyy, Petro |
collection | PubMed |
description | Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations disrupting nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts expression of POLA1, the gene encoding the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency results in increased type I interferon production. This enzyme is necessary for RNA:DNA primer synthesis during DNA replication and strikingly, POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Altogether, this work identified POLA1 as a critical regulator of the type I interferon response. |
format | Online Article Text |
id | pubmed-4836962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48369622016-09-28 DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis Starokadomskyy, Petro Gemelli, Terry Rios, Jonathan J. Xing, Chao Wang, Richard C. Li, Haiying Pokatayev, Vladislav Dozmorov, Igor Khan, Shaheen Miyata, Naoteru Fraile, Guadalupe Raj, Prithvi Xu, Zhe Xu, Zigang Ma, Lin Lin, Zhimiao Wang, Huijun Yang, Yong Ben-Amitai, Dan Orenstein, Naama Mussaffi, Huda Baselga, Eulalia Tadini, Gianluca Grunebaum, Eyal Sarajlija, Adrijan Krzewski, Konrad Wakeland, Edward K. Yan, Nan de la Morena, Maria Teresa Zinn, Andrew R. Burstein, Ezra Nat Immunol Article Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations disrupting nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts expression of POLA1, the gene encoding the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency results in increased type I interferon production. This enzyme is necessary for RNA:DNA primer synthesis during DNA replication and strikingly, POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Altogether, this work identified POLA1 as a critical regulator of the type I interferon response. 2016-03-28 2016-05 /pmc/articles/PMC4836962/ /pubmed/27019227 http://dx.doi.org/10.1038/ni.3409 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Starokadomskyy, Petro Gemelli, Terry Rios, Jonathan J. Xing, Chao Wang, Richard C. Li, Haiying Pokatayev, Vladislav Dozmorov, Igor Khan, Shaheen Miyata, Naoteru Fraile, Guadalupe Raj, Prithvi Xu, Zhe Xu, Zigang Ma, Lin Lin, Zhimiao Wang, Huijun Yang, Yong Ben-Amitai, Dan Orenstein, Naama Mussaffi, Huda Baselga, Eulalia Tadini, Gianluca Grunebaum, Eyal Sarajlija, Adrijan Krzewski, Konrad Wakeland, Edward K. Yan, Nan de la Morena, Maria Teresa Zinn, Andrew R. Burstein, Ezra DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis |
title | DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis |
title_full | DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis |
title_fullStr | DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis |
title_full_unstemmed | DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis |
title_short | DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis |
title_sort | dna polymerase-α regulates type i interferon activation through cytosolic rna:dna synthesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836962/ https://www.ncbi.nlm.nih.gov/pubmed/27019227 http://dx.doi.org/10.1038/ni.3409 |
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