Rafael Pinilla-Redondo (Rafa)
@rafomics
Asst. Prof. at Copenhagen University. Excited about phages, plasmids, and bacterial immunity!👨🔬🔬
++ For a deeper dive into the mechanism, @arturocdr.bsky.social has a fantastic thread, including a beautiful animation of the Retron IX ring! 👇💍🔥 bsky.app/profile/artu...
7/10 Our model 🧬👇 🔴OFF: RT-synthesized DNA scaffolds the ring and restrains the toxic RNase. 🟢ON: phage nucleases cut msDNA → ring collapses → RNase fires → host tRNAs shredded → infection blocked! 🛡️
6/10 Unleashed, the HEPN RNase cleaves host tRNAs indiscriminately at the anticodon loop ✂️ Protein synthesis stops & phage replication is halted, a strategy shared by many antiviral systems💥
5/10 Escaper analysis revealed the trigger: a phage-encoded nuclease (B14T) B14T snips the msDNA ✂️, the ring collapses 💥, and the RNase is released ⛓️💥. But what does it target?
4/10 In fact, early on we joked that the repeating subunits looked like Star Wars TIE fighters 🚀 Note the HEPN catalytic pocket sits exactly where the laser cannons fire... "Convergent evolution"!? 😏⚔️
3/10 CryoEM revealed an unexpected supramolecular ring, with HEPN dimers lining its inner rim, held inactive by the DNA-scaffold🔒 I imagine a fleet of "flying saucers" patrolling the cytoplasm, cannons armed & ready to fire... 🛸👽
2/10 We teamed up with @arturocdr.bsky.social (@guillermo-montoya.bsky.social's lab) to study Retron IX! The system = an RT, ncRNA, HTH–KH protein, and a toxic HEPN RNase, and provides potent defence against diverse phages ⚔️
1/10 🚨Preprint! One RING to rule them all (phages)👑💍⚔️ Bacteria build giant DNA-scaffolded RNase rings (larger than the ribosome!) to shut down viral infection🧬🧵👇 biorxiv.org/content/10.6...
Great start to the CPH MGE Computational Workshop! Awesome organization by @pentamorfico.bsky.social, @leightonpayne.bsky.social, & Dana Rorin, and a great lineup of speakers! @apcamargo.bsky.social kicking things off this morning!