MRC National Institute for Medical Research, London
Science for Health
A big role for small RNAs
23 July 2009
Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most successful human pathogens. It is estimated that a third of the world's population has been infected, with new infections occurring at a rate of approximately one per second. Although 90% of those infected do not develop any symptoms, the bacteria may persist in the form of an asymptomatic latent infection with the potential to reactivate at any time.
M. tuberculosis has to alter its physiological state to adapt to different environments encountered during latent infection, active disease and transmission. Transcriptional changes controlled by protein regulators are under active investigation in many laboratories, but the potential for RNA-based regulation has not been explored previously. There is growing evidence in other bacteria that protein-based mechanisms for transcriptional control are complemented by a post-transcriptional regulatory network dependent on small regulatory RNA (sRNA) molecules.
In studies in the lab of Douglas Young (pictured), in NIMR's Division of Mycobacterial Research, Kristine Arnvig has described a set of nine putative sRNAs identified by direct analysis of low-molecular-weight RNA molecules isolated from M. tuberculosis cultures. These include trans-acting RNAs, encoded in intergenic regions, as well as cis-acting RNAs encoded as anti-sense transcripts within open reading frames. Levels of sRNA expression are differentially regulated during different growth phases and in response to environmental stress stimuli. Overexpression of selected sRNAs has a profound effect on mycobacterial growth.
Our results provide the first demonstration that M. tuberculosis expresses sRNA molecules and that these play an important functional role in bacterial physiology. We anticipate that further functional studies in combination with sequence-based RNomics will provide novel insights into the fundamental biology of tuberculosis with the potential to inform development of improved strategies for disease control.
Douglas Young
Original article
The research findings are published in full in:
Kristine B. Arnvig and Douglas B. Young (2009)
Identification of small RNAs in Mycobacterium tuberculosis
Molecular Microbiology, epub ahead of print. Publisher abstract
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