Abstract
RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA, including long 5’ and 3’ untranslated regions, antisense transcripts, and intergenic small RNA (sRNA) molecules. More than a quarter of all sequence reads mapping outside of ribosomal RNA genes represent non-coding RNA, and the density of reads mapping to intergenic regions was more than two-fold higher than that mapping to annotated coding sequences. Selected sRNAs were found at increased abundance in stationary phase cultures and accumulated to remarkably high levels in the lungs of chronically infected mice, indicating a potential contribution to pathogenesis. The ability of tubercle bacilli to adapt to changing environments within the host is critical to their ability to cause disease and to persist during drug treatment; it is likely that novel post-transcriptional regulatory networks will play an important role in these adaptive responses.
Highlights
Mycobacterium tuberculosis presents a major threat to global health, causing around 10 million new cases of tuberculosis and 2 million deaths every year [1]
If we knew more about how the bacteria change from a harmless persistent form to an aggressive diseasecausing form, we could develop drugs that would be more effective in treating active tuberculosis and may allow us to eliminate the infection before it erupts into disease
By applying modern sequencing technologies we have discovered a new putative network of gene regulation in Mycobacterium tuberculosis that is based on RNA molecules rather than protein molecules
Summary
Mycobacterium tuberculosis presents a major threat to global health, causing around 10 million new cases of tuberculosis and 2 million deaths every year [1]. A second class of sRNAs are transcribed from a separate location on the genome – typically an intergenic region (IGR), though attenuated 5’ UTR transcripts can act as sRNAs [15] – and again influence translation and degradation of mRNAs by a more limited degree of base pairing. These ‘‘trans-encoded’’ sRNAs are functionally analogous to microRNAs in eukaryotic cells [16]
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