The ever-growing ESB molecular consortium: enter ESB2, ESB3 and ESAP1!

We are absolutely thrilled to share our latest research, published today in Nature Microbiology, uncovering a novel mechanism of specialised RNA decay in Trypanosoma brucei to fine-tune expression of virulence genes.

For decades, the parasitology field has wrestled with a stoichiometric mystery: how does the parasite produce 140-fold more VSG mRNA than the upstream ESAGs located on the same polycistronic unit?

Our group identified ESB2, a novel endonuclease localised exclusively within the Expression Site Body (ESB), the subnuclear factory where the active VSG is transcribed, which acts as a molecular filter, degrading ESAG transcripts at the source while sparing the distal VSG mRNA. Its activity is compartmentalised and spatially regulated allowing the parasite to bypass the inherent constraints of polycistronic gene organisation.

Ultimately, by tethering RNA decay to a dedicated subnuclear factory, the parasite manages its RNA levels with incredible precision. This work highlights how specialised and spatially regulated RNA decay pathways can control the expression of specific genes, particularly those involved in critical host-pathogen interactions.

This paper would have not been possible without a huge collective effort within our lab and supported by the Technology Facility at the University of York. A huge congratulations to Lianne Lansink, Leon Walther, Htay Mon Aye, and all our co-authors for the hard work and dedication.

📖 Read the full study here

✨ The Story Behind the Paper here

The stunning water colour painting was made by the super talended Laura Jeacock, check her amazing art