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• W4366997699 abstract "Abstract Vitamin B 12 (B 12 ), an essential cofactor in all domains of life, is produced de novo by only a small subset of prokaryotes, but B 12 -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 B 12 riboswitches. One controls the expression of metE , encoding a B 12 -independent methionine synthase, while the other is located upstream of ppe2, 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 by metE and ppe2 riboswitches and show that the two switches exhibit different preferences for natural isoforms of B 12 , use distinct regulatory and structural elements, and act as translational OFF switches. Based on our results, we propose that the ppe2 switch represents a new Class IIc of B 12 -sensing riboswitches. Moreover, we have identified small translated open reading frames (uORFs) upstream of both metE and ppe2 , which modulate the expression of the respective downstream genes in opposite directions. Translation of the metE riboswitch uORF suppresses MetE expression, while translation of the uORF in the ppe2 switch 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 B 12 -dependent cis -regulation in M. tuberculosis , with potential implications for host-pathogen interactions." @default.
• W4366997699 created "2023-04-27" @default.
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• W4366997699 date "2023-04-25" @default.
• W4366997699 modified "2023-10-03" @default.
• W4366997699 title "<i>Mycobacterium tuberculosis</i>employs atypical and different classes of B₁₂switches to control separate operons" @default.
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• W4366997699 doi "https://doi.org/10.1101/2023.04.25.538288" @default.
• W4366997699 hasPublicationYear "2023" @default.
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