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Publication : Nuclear RPSA senses viral nucleic acids to promote the innate inflammatory response.

First Author  Jiang Y Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  8455
PubMed ID  38114488 Mgi Jnum  J:360035
Mgi Id  MGI:7568377 Doi  10.1038/s41467-023-43784-0
Citation  Jiang Y, et al. (2023) Nuclear RPSA senses viral nucleic acids to promote the innate inflammatory response. Nat Commun 14(1):8455
abstractText  Innate sensors initiate the production of type I interferons (IFN-I) and proinflammatory cytokines to protect host from viral infection. Several innate nuclear sensors that mainly induce IFN-I production have been identified. Whether there exist innate nuclear sensors that mainly induce proinflammatory cytokine production remains to be determined. By functional screening, we identify 40 S ribosomal protein SA (RPSA) as a nuclear protein that recognizes viral nucleic acids and predominantly promotes proinflammatory cytokine gene expression in antiviral innate immunity. Myeloid-specific Rpsa-deficient mice exhibit less innate inflammatory response against infection with Herpes simplex virus-1 (HSV-1) and Influenza A virus (IAV), the viruses replicating in nucleus. Mechanistically, nucleus-localized RPSA is phosphorylated at Tyr204 upon infection, then recruits ISWI complex catalytic subunit SMARCA5 to increase chromatin accessibility of NF-kappaB to target gene promotors without affecting innate signaling. Our results add mechanistic insights to an intra-nuclear way of initiating proinflammatory cytokine expression in antiviral innate defense.
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