uORF-mediated riboregulation controls transcription of whiB7/wblC antibiotic resistance gene

Ju Hyung Lee, Eun Jin Lee, Jung Hye Roe

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

WhiB7/WblC is a transcriptional factor of actinomycetes conferring intrinsic resistance to multiple translation-inhibitory antibiotics. It positively autoregulates its own transcription in response to the same antibiotics. The presence of a uORF and a potential Rho-independent transcription terminator in the 5′ leader region has suggested a possibility that the whiB7/wblC gene is regulated via a uORF-mediated transcription attenuation. However, experimental evidence for the molecular mechanism to explain how antibiotic stress suppresses the attenuator, if any, and induces transcription of the whiB7/wblC gene has been lacking. Here we report that the 5′ leader sequences of the whiB7/wblC genes in sub-clades of actinomycetes include conserved antiterminator RNA structures. We confirmed that the putative antiterminator in the whiB7/wblC leader sequences of both Streptomyces and Mycobacterium indeed suppresses Rho-independent transcription terminator and facilitates transcription readthrough, which is required for WhiB7/WblC-mediated antibiotic resistance. The antibiotic-mediated suppression of the attenuator can be recapitulated by amino acid starvation, indicating that translational inhibition of uORF by multiple signals is a key to induce whiB7/wblC expression. Our findings of a mechanism leading to intrinsic antibiotic resistance could provide an alternative to treat drug-resistant mycobacteria.

Original languageEnglish
Pages (from-to)179-192
Number of pages14
JournalMolecular Microbiology
Volume117
Issue number1
DOIs
Publication statusPublished - 2022 Jan

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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