idanfrumkin.bsky.social
@idanfrumkin.bsky.social
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5/5
Finally, we show that random proteins can improve through beneficial mutations, enhancing RamF's efficiency as a MazF inhibitor. In summary, our work provides a mechanistic basis for how de novo gene birth produces functional proteins benefiting cells under stress.
www.nature.com/articles/s41...
4/5
If RamF inhibits MazF indirectly, why doesn't it inhibit other MazF homologs? We found that N’ terminus tagging of MazF prevents its degradation and inhibition by RamF, suggesting the N’ of MazF is critical for toxin degradation. A chimeric toxin with MazF’s N’ terminus was inhibited by RamF.
3/5
Through genetic and molecular experiments, we demonstrated that RamF modulated protein homeostasis by interacting with chaperones, leading to MazF proteolysis and loss of toxicity. Interestingly, RamF-producing cells experienced no major transcriptional changes or significant growth defects.
2/5
We identified ~2,000 random genes promoting growth, able to inhibit a variety of toxins by reducing transcription from the promoter driving toxin expression. Additionally, one random protein, named Random antitoxin of MazF (RamF), inhibited MazF specifically in a promoter-independent manner.
1/5
Can random sequences encode meaningful functions and allow de novo gene birth? To explore this, Michael Laub and I screened 100 million random genes, without sequence similarity to natural genes, for their ability to rescue growth arrest of E. coli cells producing the ribonuclease toxin MazF.
Reposted by idanfrumkin.bsky.social
relenski.bsky.social
Fascinating paper on making new genes from random sequences!

Idan Frumkin & Michael Laub. Selection of a de novo gene that can promote survival of Escherichia coli by modulating protein homeostasis pathways.

doi.org/10.1038/s415...

#Microsky #Genetics #Evolution #Microbiology
Selection of a de novo gene that can promote survival of Escherichia coli by modulating protein home...
Screening 100 million random genes, which lack homology to natural sequences, for their ability to rescue growth arrest of Escherichia coli cells caused by the toxin MazF, the authors find ~2,000 hi...
doi.org