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. |