You’ve heard of ubiquitination, meet deazaguanylation: Doug Wassarman in our lab discovered phage defense pathways have co-opted Q nucleobase biosynthetic enzymes to catalyze a new form of protein conjugation chemistry @science.org

www.science.org/doi/10.1126/...

Congratulations!!! Fantastic news!

Excited for the start of #argonautes2025 tomorrow! This year we're in Prague, @imgprague.bsky.social. Looking forward to sharing science and community with Argonaute aficionados and Argonaute Syndromes Alliance families! 🐙

Exciting work!

I'm using clariostar plus - it works perfectly

Thank you so much, Daan!

congrats!

Thank you so much for sharing, François! I posted a thread with more details on my page — very glad to share this work and would be happy to discuss it!

We describe this beautiful mechanism in our preprint:
www.biorxiv.org/content/10.1...
Huge thanks to all co-authors — and especially to my advisor, Andrey Kulbachinskiy — for invaluable support and collaboration!!!

SPARHA represents a two-component defense system based on a suicidal cellular response, in which activation of the HNH effector by the pAgo sensor leads to filament formation, promoting efficient degradation of invading nucleic acids.

We further show that activation of SPARHA by the interfering plasmid depends on the binding of guide RNAs derived from the plasmid origin of replication.

In cells, SPARHA is activated in the presence of invaders, cleaving cellular DNA and conferring protection to the bacterial population via an abortive infection mechanism.

Target DNA recognition induces conformational changes of SPARHA, freeing the HNH domains and promoting their dimerization. Subsequent association of HNH dimers leads to formation of right-handed HNH-pAgo filaments containing dimeric active sites capable of double-stranded DNA cleavage.

Unlike the DREN domain of SPARDA systems, the HNH nuclease of SPARDA is highly active in the absence of short pAgo but is kept in a silent state by pAgo until target recognition. Using SEC, TEM, AF3 modeling, and site-directed mutagenesis, we were able to reveal the activation mechanism of SPARHA.

Now, we present SPARHA, a new defense system from a distinct clade of short pAgos associated with predicted HNH nuclease effectors. SPARHA is activated after guide RNAs binding and target DNA recognition, leading to cleavage of dsDNA substrates.

Previously, we characterized the SPARDA system: a complex of short pAgo and DREN nuclease, which cleaves DNA and RNA substrates upon target DNA recognition and is activated in the presence of plasmids or phages, inducing cell death or dormancy. www.nature.com/articles/s41...

News from the world of pAgos:
We explored a distinct clade of short pAgos associated with HNH nuclease partners, which we named SPARHA, and discovered that they protect bacteria from phages and plasmids via abortive infection. Upon activation, SPARHA oligomerizes, forming filaments.
A long 🧵

Very cool (and long-awaited) structures of the Lamassu/DdmABC defense system. Seems to be another weird TA-like system?

Wait... what !? 😱
A new family of RNA-guided systems in prokaryotes ! Mind-blowing !

Congrats!!! Absolutely amazing!

What is the diversity of antiphage systems out there ?

We used protein and genomic language models (and defense score!) to start bringing some answers: >45 000 protein families.

Leb by E. Mordret.
www.biorxiv.org/content/10.1...

Interactive UMAP to have fun
mdmparis.github.io/antiphage-la...