Non-coding RNA and its potential role in Mycobacterium tuberculosis pathogenesis

Abstract

It is estimated that one third of the human population is infected with Mycobacterium tuberculosis. Efforts to understand the molecular basis of its gene regulation have been focused on identification of protein encoding genes and regulons implicated in pathogenesis. Recently, a number of studies have described the identification of several non-coding RNAs that are likely to contribute significantly to the regulatory networks responsible for adaptation and virulence in M. tuberculosis. We have reviewed emerging information on the presence and abundance of different types of non-coding RNA in M. tuberculosis and consider their potential contribution to the adaptive responses that underlie disease pathogenesis.

Figure 1. Overview of the potential roles of regulatory RNA in M. tuberculosis. The figure illustrates how different external signals, shown as orange arrows, can regulate either riboswitches, antisense or intergenic RNAs (italics). Known protein regulators, i.e., DosR and SigF as well as selected sRNAs have been indicated with names. Blue lines indicate that the resulting regulation can be either activation or inhibition; full lines indicate known activation/inhibition; dashed arrows indicate possible consequence.

Figure 2. Expression of the ino1 antisense RNA is significantly downregulated in stationary phase. The figure illustrates RNA-seq data visualized with the Artemis genome browser; reads mapping to the plus strand, i.e., antisense to ino1, are shown in red, and reads mapping to the minus strand, i.e., ino1 itself, are shown in blue. Expression levels in the two phases have been adjusted for comparative reasons.

Figure 3.M. tuberculosis riboswitches and PE-PPE genes; the figure illustrates how riboswitches in M. tuberculosis are sometimes separated from their predicted cognate mRNAs (shown in blue), by the insertion of one or more PE-PPE genes (shown in red). Due to the sequence conservation inherent in these riboswitches, the regions have been annotated as ‘conserved hypotheticals’ (shown in green). Other genes are shown in gray. The top panel shows how the B₁₂ riboswitch is separated from cobQ1 and cobU genes by a PPE2 insertion. The bottom panel shows how the Mbox has been separated from mgtC by several PE-PPE genes.