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Title: The regulatory role of sRNAs in Mycobacterium tuberculosis
Author: Houghton, J.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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The presence of small regulatory RNAs (sRNA) have now been identified in many bacteria. With the ability to regulate multiple targets at the post transcriptional level, sRNAs allow bacteria to adapt to changing environments through a regulatory step that is independent of any transcriptional signals of the target mRNAs. Previous reports show a role for sRNAs in the stress response [1]. Therefore Mycobacterium tuberculosis sRNAs could be critical for the adaptive response to the harsh environment encountered during infection. Multiple potential sRNAs have been identified in M. tuberculosis within the last few years using cDNA cloning and high throughput RNA sequencing techniques [2, 3]. Four verified sRNAs found using these two approaches, were selected for detailed investigation. The aims of the study were to identify function and interactions for the sRNAs ncRv10243, ncRv11690, ncRv12659 and ncRv13661 of Mycobacterium tuberculosis and assess their role in virulence. Transcriptomic and proteomic approaches were used to investigate sRNA expression strains for regulatory targets. Deletion and/or over expression were shown to result in changes of both mRNA and protein abundance, indicating that all candidates were functional in M. tb. Each sRNA had a varied pattern of expression, induced under a variety of stress conditions including infection. Deletion of 3 of the sRNAs however did not result in attenuation in the mouse model of infection. The challenge of characterising sRNAs demonstrates that one single technique is inadequate to identify function and a multi-pronged approach is more likely to identify direct targets.
Supervisor: Arnvig, K. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available