Anna Kanevskaya

The selfish ribosome The ribosome is responsible for protein synthesis in all cells, and is the largest energy consumer in the cell. We propose that the ribosome originated as a mutualistic symbiont of an RNA-dependent RN...

Ribosome centric perspective on the evolution of life. @mkrupovic.bsky.social and Eugene Koonin arxiv.org/abs/2602.23268

Huge thanks to my co-authors for such productive collaboration!

I am pretty sure more stories about (short) pAgos will certainly come from future studies...😊

In cells, this organization enables highly efficient elimination of cellular DNA, conferring bacterial immunity against plasmids and phages via abortive infection

Unlike SPARDA, we predict that SPARHA forms a chain of HNH domains with double active sites

Similar rearrangements leading to filament formation have been demonstrated for our first characterized system, SPARDA. doi.org/10.1038/s415... ; doi.org/10.1038/s414... ; doi.org/10.1038/s414...
Moreover, such rearrangements are also observed in other pAgos!

RNA-guide dependent target recognition induces conformational rearrangements in pAgo, causing significant shifts in the sensor loops SL1 and SL2, which in turn drive the connector loop (CL) forward and enable interactions with neighboring monomers

Our SPARHA story is out in Nature Communications!
doi.org/10.1038/s414...
We investigated a new short pAgo-HNH defense system, showing that it assembles into filaments degrading cellular DNA, inducing abortive infection, resolved their structure, and uncovered the activation mechanism 🧵

Perfect timing in the field for a beautiful review on NAD+ in bacterial immunity by @hugovaysset.bsky.social and @audeber.bsky.social @cp-molcell.bsky.social

#MicroSky

www.cell.com/molecular-ce...

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.

DNA-targeting short Argonautes complex with effector proteins for collateral nuclease activity and bacterial population immunity - Nature Microbiology DNA recognition by Argonaute proteins activates effector nucleases that trigger indiscriminate DNA and RNA cleavage and induce abortive infection.

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?

TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses RNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain o...

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...