RT Journal Article SR Electronic T1 lncRNA CARINH regulates expression and function of innate immune transcription factor IRF1 in macrophages JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202403021 DO 10.26508/lsa.202403021 VO 8 IS 3 A1 Cyr, Yannick A1 Gourvest, Morgane A1 Ciabattoni, Grace O A1 Zhang, Tracy A1 Newman, Alexandra AC A1 Zahr, Tarik A1 Delbare, Sofie A1 Schlamp, Florencia A1 Dittmann, Meike A1 Moore, Kathryn J A1 van Solingen, Coen YR 2025 UL https://www.life-science-alliance.org/content/8/3/e202403021.abstract AB The discovery of long non-coding RNAs (lncRNAs) has provided a new perspective on the centrality of RNA in gene regulation and genome organization. Here, we screened for lncRNAs with putative functions in the host response to single-stranded RNA respiratory viruses. We identify CARINH as a conserved cis-acting lncRNA up-regulated in three respiratory diseases to control the expression of its antisense gene IRF1, a key transcriptional regulator of the antiviral response. CARINH and IRF1 are coordinately increased in the circulation of patients infected with human metapneumovirus, influenza A virus, or SARS-CoV-2, and in macrophages in response to viral infection or TLR3 agonist treatment. Targeted depletion of CARINH or its mouse ortholog Carinh in macrophages reduces the expression of IRF1/Irf1 and their associated target gene networks, increasing susceptibility to viral infection. Accordingly, CRISPR-mediated deletion of Carinh in mice reduces antiviral immunity, increasing viral burden upon sublethal challenge with influenza A virus. Together, these findings identify a conserved role of lncRNA CARINH in coordinating interferon-stimulated genes and antiviral immune responses.RNA-seq and ChIRP-seq datasets have been deposited in the Gene Expression Omnibus and are available under accession numbers GSE247501, GSE261123, and GSE275288. All other data are included in the article and/or Supplemental Material.