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Reposted by Jerrin Thomas George

Nature Communications @natcomms.nature.com · 2d

Structural basis of antiphage defence by an ATPase-associated reverse transcriptase

@jerrintgeorge.bsky.social

Structural basis of antiphage defence by an ATPase-associated reverse transcriptase - Nature Communications

In this study, the authors determine the structure of a Type I-A retron from E. coli FORC82 and reveal the functional interplay between Reverse Transcriptases (RTs) and Structural Maintenance of Chromosomes (SMC) ATPases.’

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Jerrin Thomas George @jerrintgeorge.bsky.social · 9d

I am happy to share our work on the mechanism of prokaryotic immunity by a reverse transcriptase associated with an SMC-family ATPase, now published in @natcomms.nature.com
🔗 nature.com/articles/s4146…
(🧵 on the bioRxiv version ⬇️)

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Reposted by Jerrin Thomas George

Peter Fineran @peterfineran.bsky.social · Aug 18

Ever wondered why some bacteria have multiple CRISPR-Cas systems? Our new study led by Leah Smith shows how type I CRISPR systems can promote the acquisition and retention of new spacers into a co-occuring type III system. www.sciencedirect.com/science/arti...

Type I CRISPR-Cas immunity primes type III spacer acquisition

CRISPR-Cas systems are diverse, with microbes harboring multiple classes and subtypes. Type I DNA-targeting and type III RNA-targeting systems often c…

www.sciencedirect.com

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Reposted by Jerrin Thomas George

Ruben Gonzalez @rubenlgonzalez.bsky.social · Jul 31

New from our lab in @narjournal.bsky.social:
We dissect the folding dynamics of a fundamental element of RNA secondary structure—a stem-loop—at single-molecule and microsecond resolution.
doi.org/10.1093/nar/... 1/5

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Reposted by Jerrin Thomas George

Hannah Ledvina Ph.D. @hannahledvina.bsky.social · Jul 2

Words cannot describe how excited I am to share the findings from the second half of my postdoc in @aaronwhiteley.bsky.social's lab where we discover that bacteria use functional amyloids to defend themselves from predatory bacteria. rdcu.be/euu5Y. See thread for details on this epic adventure 1/.

Functional amyloid proteins confer defence against predatory bacteria

Nature - Escherichia coli uses curli fibres, oligomers of the functional amyloid CsgA, as a barrier to protect against the predatory bacteria Bdellovibrio bacteriovorus and Myxococcus xanthus in a...

rdcu.be

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Reposted by Jerrin Thomas George

Tugce Aktas @aktast.bsky.social · Jun 30

We wrote a review on Transposable Elements (TEs) and almost all aspects of TE silencing and their roles in biological processes & disease.
www.nature.com/articles/s41...

Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease - Nature Reviews Molecular Cell Biology

Transposable elements (TEs) comprise nearly half of the human genome. This Review discusses transcriptional and post-transcriptional mechanisms that repress TE activity, how TEs escape this suppressio...

www.nature.com

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Reposted by Jerrin Thomas George

Seth Shipman @seth-shipman.bsky.social · Jun 18

New Preprint!! Alejandro González-Delgado accomplished a major feat on this one: ported retron recombineering, which we love so much in E. coli, into 14 new bacterial species via a massive collaborative effort involving 9 labs!
www.biorxiv.org/content/10.1...

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Reposted by Jerrin Thomas George

Joe Peters Lab @joepeterslab.bsky.social · Jun 15

Exciting work from the Guarné lab indicating how the elusive TnsE pathway of prototypic Tn7 recognizes DNA replication features using an asymmetric dimer to integrate multiple signals at DNA replication forks linking target recognition to transposase recruitment doi.org/10.1093/nar/...

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Reposted by Jerrin Thomas George

Sternberg Lab @sternberglab.bsky.social · Jun 11

1/10 New pre-print(s) from the Sternberg Lab in collaboration with Leifu Chang's Lab! We uncover the unprecedented molecular mechanism of CRISPR-Cas12f-like proteins, which drive RNA-guided transcription independently of canonical promoter motifs.
Full story here:
www.biorxiv.org/content/10.1...

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Reposted by Jerrin Thomas George

Sternberg Lab @sternberglab.bsky.social · May 28

We're thrilled to share the published version of our DRT9 story, online today @nature.com! Congratulations to all authors!

www.nature.com/articles/s41...

Sternberg Lab @sternberglab.bsky.social · Mar 26

Hello BlueSky! Inaugural post here from the Sternberg Lab. We're excited to share our latest work, in which we teamed up with the @WiedenheftLab to study how DRT9 reverse transcriptases provide antiviral immunity. Here’s what we found: www.biorxiv.org/content/10.1...

Protein-primed DNA homopolymer synthesis by an antiviral reverse transcriptase

Bacteria defend themselves from viral predation using diverse immune systems, many of which sense and target foreign DNA for degradation. Defense-associated reverse transcriptase (DRT) systems provide...

www.biorxiv.org

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Reposted by Jerrin Thomas George

Di Jiang @dijiang319.bsky.social · May 15

@science.org 🧫🧬❄️🔬 Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis | Science www.science.org/doi/10.1126/...
@yiweichang.bsky.social www.yiweichanglab.org @jiwasa.bsky.social #virology #Influenza #Cryo-EM #StructuralBiology #RNA #polymerase

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Reposted by Jerrin Thomas George

Sorek Lab @soreklab.bsky.social · Apr 30

A beautiful discovery by Joel Tan and Philip Kranzusch, out today in Nature:

A DNA-gated molecular guard controls bacterial Hailong anti-phage defence

Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed

www.nature.com/articles/s41...

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Reposted by Jerrin Thomas George

Liz Ortiz de Ora @ortizdeora.bsky.social · Apr 18

I am thrilled to share the first manuscript from the Wiles lab! We present "Phollow", an in vivo phage-tagging approach that enables direct observation of phage outbreaks with single-virion resolution by live imaging. Here some highlights 👇 www.nature.com/articles/s41...

Phollow reveals in situ phage transmission dynamics in the zebrafish gut microbiome at single-virion resolution

Nature Microbiology - ‘Phollow’ is a live imaging-based fluorescence tagging approach that can track phage replication and spread in situ with single-virion resolution.

www.nature.com

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Reposted by Jerrin Thomas George

Aaron Whiteley @aaronwhiteley.bsky.social · Apr 8

Check out our new story led by @aesully98.bsky.social describing how bacteria turn immune evasion against phage! In collaboration with @benmorehouse.bsky.social lab, we discover that bacteria guard their nucleotide second messenger pool using a nucleotidyltransferase related to Cas10/CRISPR enzymes

Ashley Sullivan @aesully98.bsky.social · Mar 31

Excited to share that my work from the @aaronwhiteley.bsky.social lab is now on bioRxiv! With @benmorehouse.bsky.social, we discovered that the Panoptes defense system—named after the all-seeing watchman of Hera—uses decoy nucleotides to detect phage anti-defense proteins.

A minimal CRISPR polymerase produces decoy cyclic nucleotides to detect phage anti-defense proteins

Bacteria use antiphage systems to combat phages, their ubiquitous competitors, and evolve new defenses through repeated reshuffling of basic functional units into novel reformulations. A common theme ...

www.biorxiv.org

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Reposted by Jerrin Thomas George

Joe Bondy-Denomy @jbdsf.bsky.social · Apr 3

Interested in phage defenses that natively block lytic phage used in therapies?

Or do you want to figure out if a phage has a modified genome?

Meet the END-nucleases, an enzyme family that can broadly restrict phages with many diverse modifications. From talented post-doc Wearn-Xin Yee!

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

Huge thanks to the Wiedenheft Lab—especially Senuri, Murat, Quynh, Royce, Adelaide, Hannah, Adelaide, Ava and our newest faculty Steve—this work wouldn’t have been possible without your support, insight, and suggestions! 🙏

Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

I'm incredibly grateful to Blake Wiedenheft for being an amazing mentor throughout my time in his lab.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

Huge thanks to my co-first author and colleague Nate Burman, who helped me learn cryo-EM. Here’s a fantastic movie he made that captures the key mechanistic steps of this unusual immune system in action!👇

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

Altogether, our findings reveal how an RT-ATPase immune system assembles a viral surveillance complex using a cDNA ‘harpoon’. Phage flap nucleases trigger its activation, leading to tRNA depletion and translation arrest—while phages fight back by encoding their own tRNAs.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

Interestingly phages evade this ATPase-associated RT immune system by encoding their own tRNA-Ser genes! Comparison between phage encoded tRNA-Ser and E.coli tRNA-Ser revealed major differences clustered in the D-loop, which is key for recognition by aminoacyl tRNA synthetase.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

Upon co-expressing the retron with phage flap nuclease, we observed nucleoid compaction in E. coli—a hallmark of translation arrest—driven by HNH-mediated depletion of tRNA-Ser. Recently Azam et al. (Nov 24) showed that expression of ATPase+HNH from Eco7 retron depletes tRNA-Tyr.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

We then asked: what triggers this system? By sequencing phages that survive retron defense and expressing candidate genes, we found that phage-encoded flap nucleases (yes! the ones that remove Okazaki fragments) are baited to cleave the cDNA scaffold, activating the complex.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

We find that HNH is recruited asymmetrically, either in an up or down orientation relative to the RT, and is anchored by a specialized C-terminal claw formed by the ATPase homodimer. Mutations at the ATPase–HNH interface or in claw-stabilizing residues abolished defense.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

The long coiled-coil domains of SMC-family ATPases—which typically wrap DNA in repair complexes like Rad50—facilitate interdimer contacts in the retron complex, forming 'bear hug' and 'dorsal fin'-like structures that flank either end of the cDNA scaffold.

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Jerrin Thomas George @jerrintgeorge.bsky.social · Mar 27

Using cryo-EM, we determined that this immune system forms a 364 kDa phage surveillance complex where the extrachromosomal cDNA—made by the RT using the ncRNA—acts as a molecular scaffold to recruit two ATPase homodimers and the nuclease.

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