ArticleMolecular microbiology2020
Polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression in mycobacteria.
Article in Molecular microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Genome scale CRISPRi reveals both shared and strain-specific vulnerabilities in genetically diverse drug-resistant strains of Mycobacterium tuberculosis.Nature communications · 2026Article
- Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis.Nature microbiology · 2026Article
- Fred Goldberg machines in the pathogenesis of Mycobacterium tuberculosis.The Journal of biological chemistry · 2026Review
- Harnessing toxin-mediated ribosome stalling as a complementary tool to annotate bacterial ORFs.Nucleic acids research · 2026Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- The BR-body proteome contains a complex network of protein-protein and protein-RNA interactions.Cell reports · 2023Article
- The BR-body proteome contains a complex network of protein-protein and protein-RNA interactions.bioRxiv : the preprint server for biology · 2023Article
- Article
- Miniprep assisted proteomics (MAP) for rapid proteomics sample preparation.Analytical methods : advancing methods and applications · 2023Article
- Mycobacterium smegmatis: The Vanguard of Mycobacterial Research.Journal of bacteriology · 2023Review
- In vitro studies of the protein-interaction network of cell-wall lytic transglycosylase RlpA of Pseudomonas aeruginosa.Communications biology · 2022Article
- Proteo-genetic analysis reveals clear hierarchy of ESX-1 secretion inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Regulation of Leaderless mRNA Translation in Bacteria.Microorganisms · 2022Review
- Pervasive translation ineLife · 2022Article
- Small Proteins in Archaea, a Mainly Unexplored World.Journal of bacteriology · 2022Review
- Article
- A snapshot of translation in Mycobacterium tuberculosis during exponential growth and nutrient starvation revealed by ribosome profiling.Cell reports · 2021Article
- The genetic proteome: Using genetics to inform the proteome of mycobacterial pathogens.PLoS pathogens · 2021Review
- A global data-driven census ofmicroLife · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Genome-wide transcriptomic analyses have revealed abundant expressed short open reading frames (ORFs) in bacteria. Whether these short ORFs, or the small proteins they encode, are functional remains an open question. One quarter of mycobacterial mRNAs are leaderless, beginning with a 5'-AUG or GUG initiation codon. Leaderless mRNAs often encode unannotated short ORFs as the first gene of a polycistronic transcript. Here, we show that polycysteine-encoding leaderless short ORFs function as cysteine-responsive attenuators of operonic gene expression. Detailed mutational analysis shows that one polycysteine short ORF controls expression of the downstream genes. Our data indicate that ribosomes stalled in the polycysteine tract block mRNA structures that otherwise sequester the ribosome-binding site of the 3'gene. We assessed endogenous proteomic responses to cysteine limitation in Mycobacterium smegmatis using mass spectrometry. Six cysteine metabolic loci having unannotated polycysteine-encoding leaderless short ORF architectures responded to cysteine limitation, revealing widespread cysteine-responsive attenuation in mycobacteria. Individual leaderless short ORFs confer independent operon-level control, while their shared dependence on cysteine ensures a collective response mediated by ribosome pausing. We propose the term ribulon to classify ribosome-directed regulons. Regulon-level coordination by ribosomes on sensory short ORFs illustrates one utility of the many unannotated short ORFs expressed in bacterial genomes.
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