Research group Group Mannervik

Recent research published in Nucleic Acids Research has uncovered a novel role for small nucleolar RNAs (snoRNAs) in the transcriptional regulation of the anti-viral response. Traditionally, snoRNAs are known for their role in ribosomal biogenesis. Here, the Visa group at the Department of Molecular Biosciences, Wenner-Gren Institute (MBW) at Stockholm University, in collaboration with researchers from various Swedish universities, has demonstrated that snoRNAs also participate in the regulating chromatin accessibility to influence gene transcription profiles. In this study, the fruit fly Drosophila melanogaster was used as a model organism to investigate the regulation of immune responses. When fruit flies are infected with viruses, the host’s cellular machinery is activated, which triggers an effective immune response. U3 small nucleolar RNA (U3 snoRNA) is one of the genes induced during this process. The induced U3 snoRNA helps maintain an open chromatin conformation, thereby facilitating the transcription of various immune pathway genes. U3 snoRNA acts by recruiting the SWI/SNF chromatin remodeler, Brahma, to immune genes. If U3 snoRNA is knocked out, fruit fly larvae fail to efficiently fight viral infections and die during late larval development. Not only does U3 snoRNA facilitate immune gene activation, but it also promotes the chromatin remodelling needed for immune gene expression, establishing it as a key regulator of the antiviral response.

A study published in Molecular Cell reveals that both CBP’s presence and its enzymatic function are essential for proper gene activation at the start of development. Disruptions in this process lead to severe developmental defects, the study shows.

The transcriptional co-activator p300/CBP is involved in gene activation by acetylating histones and other proteins. It can also stimulate transcription by helping RNA polymerase to find the promoter and initiate transcription. George Hunt, Ann Boija and Mattias Mannervik have discovered that this non-enzymatic function of p300/CBP is involved in epigenetic silencing. Recruitment of RNA polymerase to silent gene regions is necessary for nucleosome depletion and formation of RNA-DNA hybrids (R-loops), which allows Polycomb proteins to associated with and maintain these genes in a silent state.