A U3 snoRNA is required for the regulation of chromatin dynamics and antiviral response in Drosophila melanogaster.

Jain S, Planells J, Regadas I, Barrett D, von Euler A, Sinha I, Lindberg BG, Hesson JC, Swacha P, Gekara NO, Pelechano V, Engström Y, Mannervik M, Visa N

Nucleic Acids Res. 53 (14) - [2025-07-19; online 2025-07-30]

Small nucleolar RNAs (snoRNAs) are prevailing components of the chromatin-associated transcriptome. Here we show that specific snoRNAs are required for the activation of immune response genes and for survival during viral infections in Drosophila melanogaster. We have studied snoRNA:U3:9B, a chromatin-associated snoRNA that binds to a large number of protein coding genes, including immune response genes. We have used CRISPR/Cas9 to delete snoRNA:U3:9B and study its function in vivo. SnoRNA:U3:9B-deficient larvae are viable but failed to develop into pupae when challenged by expression of a Sindbis virus replicon. SnoRNA:U3:9B is localized to immune genes in vivo and the chromatin decompaction and gene activation typically observed at immune genes following infection are abolished in snoRNA:U3:9B-deficient larvae, which suggests that this snoRNA acts locally to regulate chromatin accessibility. Mechanistically, snoRNA:U3:9B is required for the recruitment of the chromatin remodeler Brahma to a set of target immune genes. In summary, these results uncover an antiviral defense mechanism that relies on a snoRNA for the recruitment of a chromatin remodeling factor to immune genes to facilitate immune gene activation.

PubMed 40737091

DOI 10.1093/nar/gkaf715

Crossref 10.1093/nar/gkaf715

pmc: PMC12309367
pii: 8219220