384: RNA Brake on Cholera Phage: CisR Controls CTXϕ

Haycocks JRJ et al., PNAS - This episode examines the discovery of CisR, a small RNA produced from the 3’UTR of prtV in Vibrio cholerae, which posttranscriptionally represses the CTXϕ-encoded cep mRNA via Hfq-mediated base-pairing. CisR accumulation is controlled by HapR and CRP and processed by RNase E, linking quorum sensing and carbon status to phage activation. We discuss the experimental evidence showing CisR lowers Cep protein levels and limits CTXϕ production under induction conditions. Key terms: small RNA, CTXϕ, Vibrio cholerae, Hfq, quorum sensing.

Study Highlights:
Researchers identified CisR as a ~50-nt sRNA derived from the 3’UTR of prtV that requires RNase E for processing and Hfq for stability and action. RIL-seq and reporter assays show CisR base-pairs with the cep mRNA ribosome binding site to inhibit translation, and deletion or overexpression of cisR respectively increases or decreases Cep levels and extracellular CTXϕ DNA after induction. Transcription of the vca0224-prtV-cisR operon is directly activated by HapR and CRP, linking CisR to quorum sensing and carbon catabolite signals. The work positions a core-genome sRNA as a posttranscriptional regulator that modulates a horizontally acquired phage life cycle.

Conclusion:
CisR is a 3’UTR-derived sRNA that integrates cell-density and metabolic signals to repress CTXϕ coat protein production via Hfq-dependent base-pairing with cep, thereby limiting phage production under stress and coordinating phage activation with host physiology.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
A 3’UTR-derived small RNA modulates the life cycle of the cholera toxin–encoding filamentous phage, CTXϕ

First author:
Haycocks JRJ

Journal:
PNAS

DOI:
10.1073/pnas.2535142123

Reference:
Haycocks JRJ, O’Driscoll E, Sprenger M, Thriene K, Jung E-M, Siemers M, Lippegaus A, Krautwurst S, Grainger DC, Papenfort K. A 3’UTR-derived small RNA modulates the life cycle of the cholera toxin–encoding filamentous phage, CTXϕ. PNAS. 2026;123(23):e2535142123. doi:10.1073/pnas.2535142123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/cisr-controls-ctxphi-life-cycle

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-06-03.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantively audited the transcript sections describing CisR origin, CisR-cep interaction, HapR/CRP regulation, RIL-seq mapping, and functional impact on CTXϕ production under induction conditions.
- transcript topics: CTXϕ life cycle and filamentous phage biology; CisR discovery from prtV 3’UTR and RNase E processing; HFQ and RIL-seq methodology to map RNA interactions; CisR-cep base-pairing and translational repression; HapR and CRP regulation of prtV-cisR transcription; CisR impact on CTXϕ production during MMC induction

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- CisR is produced from the 3’...