Small RNA profiling in Mycobacterium tuberculosis identifies MrsI as necessary for an anticipatory iron sparing response
| Autor: | Michael R. Chase, Rushdy Ahmad, Vincent H Lin, Thibault Barbier, Jonathan Livny, Matthew J. Szucs, Brian Tjaden, Sarah M. Fortune, Raylin Xu, Jeremy M. Rock, Josie François, Elias R. Gerrick |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
iron sparing Small RNA Tuberculosis Iron RNA-Seq Computational biology Microbiology Mycobacterium tuberculosis 03 medical and health sciences Gene expression medicine small RNA Pathogen Multidisciplinary biology Sequence Analysis RNA Gene Expression Profiling riboregulation Gene Expression Regulation Bacterial Biological Sciences biology.organism_classification medicine.disease 3. Good health Gene expression profiling RNA Bacterial 030104 developmental biology Regulon RNA Small Untranslated |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1718003115 |
| Popis: | Significance This work describes the most extensive discovery and functional characterization of small regulatory RNAs (sRNAs) in Mycobacterium tuberculosis to date. We comprehensively define the sRNAs expressed in M. tuberculosis under five host-like stress conditions. This reference dataset comprehensively defines the expression patterns and boundaries of mycobacterial sRNAs. We perform in-depth characterization of one sRNA, mycobacterial regulatory sRNA in iron (MrsI), which is induced in M. tuberculosis in multiple stress conditions. MrsI is critical for the iron-sparing response in mycobacteria by binding directly to mRNAs encoding nonessential iron-containing proteins to repress their expression. Interestingly, MrsI acts in an anticipatory manner, in which its induction by a variety of stresses primes M. tuberculosis to enter an iron-sparing state more rapidly upon iron deprivation. One key to the success of Mycobacterium tuberculosis as a pathogen is its ability to reside in the hostile environment of the human macrophage. Bacteria adapt to stress through a variety of mechanisms, including the use of small regulatory RNAs (sRNAs), which posttranscriptionally regulate bacterial gene expression. However, very little is currently known about mycobacterial sRNA-mediated riboregulation. To date, mycobacterial sRNA discovery has been performed primarily in log-phase growth, and no direct interaction between any mycobacterial sRNA and its targets has been validated. Here, we performed large-scale sRNA discovery and expression profiling in M. tuberculosis during exposure to five pathogenically relevant stresses. From these data, we identified a subset of sRNAs that are highly induced in multiple stress conditions. We focused on one of these sRNAs, ncRv11846, here renamed mycobacterial regulatory sRNA in iron (MrsI). We characterized the regulon of MrsI and showed in mycobacteria that it regulates one of its targets, bfrA, through a direct binding interaction. MrsI mediates an iron-sparing response that is required for optimal survival of M. tuberculosis under iron-limiting conditions. However, MrsI is induced by multiple host-like stressors, which appear to trigger MrsI as part of an anticipatory response to impending iron deprivation in the macrophage environment. |
| Databáze: | OpenAIRE |
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