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Nearly one third of the world’s population is infected with  Mycobacterium tuberculosis  ( Mtb ). While much work has focused on the role of different  Mtb  encoded proteins in pathogenesis, recent studies have revealed that  Mtb  also transcribes many noncoding RNAs whose functions remain poorly characterized. We performed RNA sequencing and identified a subset of  Mtb  H37Rv-encoded small RNAs (<30 nts in length) that were produced in infected macrophages. Designated as smaller noncoding RNAs (sncRNAs), three of these predominated the read counts. Each of the three, sncRNA-1, sncRNA-6, and sncRNA-8 had surrounding sequences with predicted stable secondary RNA stem loops. Site-directed mutagenesis of the precursor sequences suggest the existence of a hairpin loop dependent RNA processing mechanism. A functional assessment of sncRNA-1 suggested that it positively regulated two mycobacterial transcripts involved in oleic acid biosynthesis. Complementary loss- and gain- of-function approaches revealed that sncRNA-1 positively supports  Mtb  growth and survival in nutrient-depleted cultures as well as in infected macrophages. Overall, the findings reveal that  Mtb  produces sncRNAs in infected cells, with sncRNA-1 modulating mycobacterial gene expression including genes coupled to oleic acid biogenesis.

frontiers in microbiology

sncRNA-1 Is a Small Noncoding RNA Produced by Mycobacterium tuberculosis in Infected Cells That Positively Regulates Genes Coupled to Oleic Acid Biosynthesis