Viruses are adept at entering cells and using RNA or DNA to commandeer cellular systems to make more viruses. Happily, our mammalian cells are skilled at fighting these invaders, and the interferon system is a major tool in the defensive arsenal. Now, perhaps you (like me) tend to think of viruses as invaders from outside the cell; in fact, zillions of viral troublemakers live in our genomes (“the call is coming from inside the house!”), among them the fascinating and ubiquitous retrotransposons. Interferons are deployed against them, too, which is great as long as the system can avoid damaging friendly RNA (and DNA) when fighting intruders. A recent preprint explores a new player in this tense drama: a protein (called DGCR8) that helps with generation of microRNAs, now apparently moonlighting in the control of the interferon system.
The authors show that removing DGCR8 causes cells to ramp up their interferon responses, and dangerously so: a human syndrome that lacks one copy of the gene is associated with increased interferon responses that lead to autoimmune effects. (This is DiGeorge syndrome, which gives DGCR8 its seemingly nondescript name.) Using cells from that syndrome, the authors show a clear relationship between DGCR8 expression and interferon activity. In short, this protein seems to be a big player in the struggle between our cells and rogue genetic elements (viruses, inside and out).
The science is cool, and so are the authors’ descriptions. Consider the beginning of their abstract:
The type I interferon (IFN) response is the main innate immune pathway against viruses in mammals. This pathway must be tightly regulated to prevent viral spread while avoiding excessive immune responses. Here, we show that inactivation of the double stranded RNA (dsRNA)-binding protein DGCR8 unleashes the IFN response in human cells.
Unleashes! A good abstract is clear and compelling. Like this one.
Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8
In bioRxiv, 30 May 2025
From the groups of Sara R. Heras at the University of Granada and Sara Macias at the University of Edinburgh
Snippet by Stephen Matheson
Image credit: Figure 3 from Gázquez-Gutiérrez et al., “Sensing of transposable elements by the antiviral innate immune system,” RNA (2021) (CC BY)