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Expression, maturation and turnover of DrrS, an unusually stable, DosR regulated small RNA in Mycobacterium tuberculosis

Moores, Alexandra, Riesco, Ana B., Schwenk, Stefan, Arnvig, Kristine B. (2017) Expression, maturation and turnover of DrrS, an unusually stable, DosR regulated small RNA in Mycobacterium tuberculosis. PLoS ONE, 12 (3). pp. 1-27. E-ISSN 1932-6203. (doi:10.1371/journal.pone.0174079) (KAR id:81097)

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Mycobacterium tuberculosis depends on the ability to adjust to stresses encountered in a range of host environments, adjustments that require significant changes in gene expression. Small RNAs (sRNAs) play an important role as post-transcriptional regulators of prokaryotic gene expression, where they are associated with stress responses and, in the case of pathogens, adaptation to the host environment. In spite of this, the understanding of M. tuberculosis RNA biology remains limited. Here we have used a DosR-associated sRNA as an example to investigate multiple aspects of mycobacterial RNA biology that are likely to apply to other M. tuberculosis sRNAs and mRNAs. We have found that accumulation of this particular sRNA is slow but robust as cells enter stationary phase. Using reporter gene assays, we find that the sRNA core promoter is activated by DosR, and we have renamed the sRNA DrrS for DosR Regulated sRNA. Moreover, we show that DrrS is transcribed as a longer precursor, DrrS+, which is rapidly processed to the mature and highly stable DrrS. We characterise, for the first time in mycobacteria, an RNA structural determinant involved

in this extraordinary stability and we show how the addition of a few nucleotides can lead to acute destabilisation. Finally, we show how this RNA element can enhance expression of a heterologous gene. Thus, the element, as well as its destabilising derivatives may be employed to post-transcriptionally regulate gene expression in mycobacteria in combination with different promoter variants. Moreover, our findings will facilitate further investigations into the severely understudied topic of mycobacterial RNA biology and into the role that regulatory RNA plays in M. tuberculosis pathogenesis.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0174079
Uncontrolled keywords: Mycobacterium tuberculosis; sRNA; DrrS+
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Alexandra Moores
Date Deposited: 01 May 2020 16:02 UTC
Last Modified: 04 May 2020 12:52 UTC
Resource URI: (The current URI for this page, for reference purposes)
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