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Happy to share our new preprint about how we solved the mystery of some of the coolest bacterial elements:
Retrons function as anti-phage defense systems!
https://biorxiv.org/cgi/content/short/2020.06.21.156273v1
See thread below by the 3 of us: @AdiMillman @AudeBer @AAvihail
Retrons function as anti-phage defense systems!
https://biorxiv.org/cgi/content/short/2020.06.21.156273v1
See thread below by the 3 of us: @AdiMillman @AudeBer @AAvihail
It all started from a peculiar observation. At the @SorekLab, we look for new anti-phage defense mechanisms. While studying a novel anti-phage operon composed of an RT and ATPase, we noticed a large intergenic region between these 2 genes.
Could it contain a non-coding RNA?
Could it contain a non-coding RNA?
RNA-seq confirmed the existence
of a non coding RNA! A deeper analysis revealed that this RNA has typical features of a retron-type ncRNA.
But... what is a retron?
of a non coding RNA! A deeper analysis revealed that this RNA has typical features of a retron-type ncRNA.
But... what is a retron?
Retrons are bacterial genetic elements comprised of a reverse transcriptase (RT) and a non-coding RNA. The RT uses the non-coding RNA as a template, generating a chimeric RNA/DNA molecule. Although retrons were discovered over three decades ago, their function remained unknown.
So we discovered a new anti-phage system that encodes a retron! But are all retrons involved in phage defense? A bioinformatic analysis revealed that retrons come within systems. These retrons are encoded in defense islands, a predictor of the anti-phage function.
So we took a bunch of retrons,
cloned them and tested them against a range of E. coli phages.
Guess what? Defense!
cloned them and tested them against a range of E. coli phages.
Guess what? Defense!
Then we wanted to know more about how retrons protect against phage. So we isolated phage mutants that escape Ec48 retron defense. Several single mutations allowed the phage to overcome the retron defense. They mostly fell into proteins that are RecBCD inhibitors.
Finally, additional experiments
led us to a mechanistic model in which the Ec48 retron “guards” the normal activity of the immune hub RecBCD. Inactivation of RecB by phage inhibitors triggers the retron system and leads to cell suicide before the phage is able to replicate.
led us to a mechanistic model in which the Ec48 retron “guards” the normal activity of the immune hub RecBCD. Inactivation of RecB by phage inhibitors triggers the retron system and leads to cell suicide before the phage is able to replicate.
A fascinating thing about
the retron immune strategy is the concept similarity to the “guard hypothesis” in plant immunity.
Plant proteins guard central cellular processes and detect their disruption by pathogen effectors as a signature for infection: https://www.nature.com/articles/s41564-019-0623-2?proof=true
the retron immune strategy is the concept similarity to the “guard hypothesis” in plant immunity.
Plant proteins guard central cellular processes and detect their disruption by pathogen effectors as a signature for infection: https://www.nature.com/articles/s41564-019-0623-2?proof=true
As we were working on this study, we realized at a conference at @embl that the @TypasLab was also elucidating the mysteries of retrons. Check out their amazing new work that complements ours:
https://www.biorxiv.org/content/10.1101/2020.06.22.160242v1
https://www.biorxiv.org/content/10.1101/2020.06.22.160168v1
https://www.biorxiv.org/content/10.1101/2020.06.22.160242v1
https://www.biorxiv.org/content/10.1101/2020.06.22.160168v1
And last but not least, this work was a crazy fun collaboration between
@AdiMillman @AudeBer @AAvihail that managed to continue even during
the pandemic.
#WomenInSTEM
@AdiMillman @AudeBer @AAvihail that managed to continue even during
the pandemic.
#WomenInSTEM
That's it, we hope you'll now share our passion for retrons...
