@anemudraia.bsky.social and I are grateful to our very first team members, Veronica, Yimo, and Riley, who bravely joined the lab early on and worked hard on this project!

And big thanks to our collaborators, @lloeff.bsky.social and @kirillemedvedev.bsky.social. Excited for what’s next!

Our work highlights Schlafens as an ancient, mechanistically conserved family of immune effectors, revealing the deep evolutionary origin of tRNA-targeting antiviral immunity in humans.

We focused on a system, which we named pSlfn5, that senses tail assembly chaperones of T5-like phages and cleaves tRNA, triggering abortive infection.

We show that its sensor domains are modular and can be swapped to engineer phage specificity.

We found Schlafen nucleases are widespread in prokaryotes, enriched in phage defense islands, and protect bacteria from phage infection.

Prokaryotic Schlafens are fused to diverse domains that likely act as phage sensors and regulate nuclease activity.

We asked: How deep are the evolutionary roots of Schlafen antiviral tRNA‑cleaving mechanism? 🤔

Schlafen proteins were discovered in 1998 and named after the German verb for “to sleep” because they induce dormancy when overexpressed in mouse cells.

Among many other functions, mammalian Schlafens restrict viruses by cleaving tRNAs and shutting down translation.