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The conserved transcriptional repressor SP140 inhibits interferon-\u03b2 (\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    ) expression through an unknown mechanism\n                    <jats:sup>3,4<\/jats:sup>\n                    . Here we report that SP140 does not directly repress\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    transcription. Instead, SP140 negatively regulates\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    mRNA stability by directly repressing the expression of a previously uncharacterized regulator that we call RESIST (regulated stimulator of interferon via stabilization of transcript; previously annotated as annexin 2 receptor). RESIST promotes\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    mRNA stability by counteracting\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    mRNA destabilization mediated by the tristetraprolin (TTP) family of RNA-binding proteins and the CCR4\u2013NOT deadenylase complex. SP140 localizes within punctate structures called nuclear bodies that have important roles in silencing DNA-virus gene expression in the nucleus\n                    <jats:sup>3<\/jats:sup>\n                    . Consistent with this observation, we find that SP140 inhibits replication of the gammaherpesvirus MHV68. The antiviral activity of SP140 is independent of its ability to regulate\n                    <jats:italic>Ifnb1<\/jats:italic>\n                    . Our results establish dual antiviral and interferon regulatory functions for SP140. We propose that SP140 and RESIST participate in antiviral effector-triggered immunity\n                    <jats:sup>5,6<\/jats:sup>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41586-025-09152-2","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:02:09Z","timestamp":1749639729000},"page":"1372-1380","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["SP140\u2013RESIST pathway regulates interferon mRNA stability and antiviral immunity"],"prefix":"10.1038","volume":"643","author":[{"given":"Kristen C.","family":"Witt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Dziulko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohyun","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-6452","authenticated-orcid":false,"given":"Filip","family":"Pekovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-7268","authenticated-orcid":false,"given":"Arthur Xiuyuan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5463-3055","authenticated-orcid":false,"given":"Grace Y.","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3940-7807","authenticated-orcid":false,"given":"Ophelia Vosshall","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9649-8231","authenticated-orcid":false,"given":"Azra","family":"Lari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz M.","family":"Gaidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4899-4414","authenticated-orcid":false,"given":"Stefan A.","family":"Fattinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preethy","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmandeep","family":"Dhaliwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-1503","authenticated-orcid":false,"given":"Dmitri I.","family":"Kotov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Coscoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0479-9377","authenticated-orcid":false,"given":"Britt A.","family":"Glaunsinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3721-1739","authenticated-orcid":false,"given":"Eugene","family":"Valkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5392-937X","authenticated-orcid":false,"given":"Edward B.","family":"Chuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6686-3912","authenticated-orcid":false,"given":"Russell E.","family":"Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"9152_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nri3787","volume":"15","author":"F McNab","year":"2015","unstructured":"McNab, F. et al. 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