Premature termination of transcription is shaped by Rho and translated uORFS in Mycobacterium tuberculosis

D’Halluin, Alexandre; Polgar, Peter; Kipkorir, Terry; Patel, Zaynah; Cortes, Teresa; Arnvig, Kristine B.

doi:10.1016/j.isci.2023.106465

Cited by 9 publications

(15 citation statements)

References 63 publications

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“…The TTS patterns within these two leaders indicated multiple TTS thoughout the metE leader, compared to two, closely spaced TTS in the ppe2 leader, suggesting differences in the regulation of the switches (Fig. 2A & B) (21). To explore how B 12 might affect growth and metE and ppe2 transcription, we grew cultures of M. tuberculosis to OD 600 ~0.6 before adding 10 μg/mL AdoB 12 ; notably, this did not affect the growth rate (Supplementary Fig.…”

Section: Premature Transcription Termination In Mete and Ppe2 Leadersmentioning

confidence: 97%

“…We have mapped multiple premature transcription termination sites (TTS) associated with RNA leaders including those of metE and ppe2 in M. tuberculosis cultures grown in standard conditions (21). The TTS patterns within these two leaders indicated multiple TTS thoughout the metE leader, compared to two, closely spaced TTS in the ppe2 leader, suggesting differences in the regulation of the switches (Fig.…”

Section: Premature Transcription Termination In Mete and Ppe2 Leadersmentioning

confidence: 99%

“…M. tuberculosis encodes numerous short, translated ORFs (uORFs) upstream of annotated genes including genes controlled by riboswitches (21,69). The metE riboswitch encodes four potentially translated uORFs (umetE1-4) based on credible SD sequences and associated start codons at +88 (CUG), +123 (UUG), +140 (CUG), & +187 (GUG), relative to the TSS (Fig.…”

Section: A Short Translated Orf Within the Mete Aptamer Suppresses Me...mentioning

confidence: 99%

“…The absence of translation may in turn expose RUT sites on the mRNA, facilitating Rho-dependent transcription termination (16,(18)(19)(20). Intrinsic terminators are rare in mycobacteria and therefore, mycobacterial riboswitches are presumably mostly translational and/or Rho-dependent (4,21).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it has been proposed that codons and/or peptides arising from the translation of so-called upstream open reading frames (uORFs) occurring within gene leaders can either positively or negatively impact the expression level of the downstream ORF (21,(60)(61)(62). For example, the presence of translating ribosomes on uORFs in mRNA 5' regions can modulate the expression of the downstream gene by inducing or suppressing premature transcription termination, or by interfering with translation initiation of the downstream ORF (63).…”

Section: Introductionmentioning

confidence: 99%

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Mycobacterium tuberculosisemploys atypical and different classes of B₁₂switches to control separate operons

Kipkorir

Polgar

Barker

et al. 2023

Preprint

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Vitamin B12 (B12), an essential cofactor in all domains of life, is produced de novo by only a small subset of prokaryotes, but B12-sensing riboswitches are some of the most widely distributed riboswitches in bacteria.Mycobacterium tuberculosis, the causative agent of the ongoing tuberculosis pandemic, encodes two distinct vitamin B12 riboswitches. One controls the expression ofmetE, encoding a B12-independent methionine synthase, while the other is located upstream ofppe2, a PE/PPE family gene whose function is still unresolved. Here, we analyse ligand sensing, secondary structure architecture, and gene expression control mechanisms of these two riboswitches. Our results provide the first evidence of direct ligand binding bymetEandppe2riboswitches and show that the two switches exhibit different preferences for natural isoforms of B12, use distinct regulatory and structural elements, and act as translational OFF switches. Based on our results, we propose that theppe2switch represents a new Class IIc of B12-sensing riboswitches. Moreover, we have identified small translated open reading frames (uORFs) upstream of bothmetEandppe2, which modulate the expression of the respective downstream genes in opposite directions. Translation of themetEriboswitch uORF suppresses MetE expression, while translation of the uORF in theppe2switch is essential for PPE2 expression via the synthesis of a uORF-PPE2 fusion protein. In summary, our findings reveal an unexpected diversity and complexity of B12-dependent cis-regulation inM. tuberculosis, with potential implications for host-pathogen interactions.

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Section: Premature Transcription Termination In Mete and Ppe2 Leadersmentioning

confidence: 97%

Section: Premature Transcription Termination In Mete and Ppe2 Leadersmentioning

confidence: 99%

Section: A Short Translated Orf Within the Mete Aptamer Suppresses Me...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mycobacterium tuberculosisemploys atypical and different classes of B₁₂switches to control separate operons

Kipkorir

Polgar

Barker

et al. 2023

Preprint

Self Cite

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Phase Variation of Flagella and Toxins in Clostridioides difficile is Mediated by Selective Rho-dependent Termination

Warren Norris,

Plaskon,

Tamayo

2024

Journal of Molecular Biology

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Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis

et al. 2023

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Premature termination of transcription is shaped by Rho and translated uORFS in Mycobacterium tuberculosis

Cited by 9 publications

References 63 publications

Mycobacterium tuberculosisemploys atypical and different classes of B₁₂switches to control separate operons

Mycobacterium tuberculosisemploys atypical and different classes of B₁₂switches to control separate operons

Phase Variation of Flagella and Toxins in Clostridioides difficile is Mediated by Selective Rho-dependent Termination

Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis

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Premature termination of transcription is shaped by Rho and translated uORFS in Mycobacterium tuberculosis

Cited by 9 publications

References 63 publications

Mycobacterium tuberculosisemploys atypical and different classes of B12switches to control separate operons

Mycobacterium tuberculosisemploys atypical and different classes of B12switches to control separate operons

Phase Variation of Flagella and Toxins in Clostridioides difficile is Mediated by Selective Rho-dependent Termination

Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis

Contact Info

Product

Resources

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Mycobacterium tuberculosisemploys atypical and different classes of B₁₂switches to control separate operons

Mycobacterium tuberculosisemploys atypical and different classes of B₁₂switches to control separate operons