Shutoff of host transcription triggers a toxin-antitoxin system to cleave phage RNA and abort infection
Name
nihms-1723064.pdf
Description
Accepted version
Size
2.68 MB
Format
Adobe PDF
Checksum (MD5)
e7018d86e64a5c49723d8b0fc8fa69c9
Author(s)
Guegler, Chantal K
Laub, Michael T
Date Issued
2021
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Guegler, Chantal K and Laub, Michael T. 2021. "Shutoff of host transcription triggers a toxin-antitoxin system to cleave phage RNA and abort infection." Molecular Cell, 81 (11).
Version
Author's final manuscript
Abstract
Toxin-antitoxin (TA) systems are widespread in bacteria, but their activation mechanisms and bona fide targets remain largely unknown. Here, we characterize a type III TA system, toxIN, that protects E. coli against multiple bacteriophages, including T4. Using RNA sequencing, we find that the endoribonuclease ToxN is activated following T4 infection and blocks phage development primarily by cleaving viral mRNAs and inhibiting their translation. ToxN activation arises from T4-induced shutoff of host transcription, specifically of toxIN, leading to loss of the intrinsically unstable toxI antitoxin. Transcriptional shutoff is necessary and sufficient for ToxN activation. Notably, toxIN does not strongly protect against another phage, T7, which incompletely blocks host transcription. Thus, our results reveal a critical trade-off in blocking host transcription: it helps phage commandeer host resources but can activate potent defense systems. More generally, our results now reveal the native targets of an RNase toxin and activation mechanism of a phage-defensive TA system.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2021.03.027
