Jain, S., Planells, J., Regadas, I., Barrett, D., von Euler, A., Sinha, I., Lindberg, B.G., Hesson, J.C., Swacha, P., Gekara, N.O., Pelechano, V., Engström, Y., Mannervik, M., Visa, N. (2025). A U3 snoRNA is required for the regulation of chromatin dynamics and antiviral response in Drosophila melanogaster.  Nucleic Acids Res. 53(14): gkaf715.

FBrf0263077

Research paper

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.

PMC12309367 (PMC) (EuropePMC)