Regulatory RNA in Mycobacterium tuberculosis, back to basics

Abstract

Since the turn of the millenium, RNA-based control of gene expression has added an extra dimension to the central dogma of molecular biology. Still, the roles of Mycobacterium tuberculosis regulatory RNAs and the proteins that facilitate their functions remain elusive, although there can be no doubt that RNA biology plays a central role in the baterium's adaptation to its many host environments. In this review, we have presented examples from model organisms and from M. tuberculosis to showcase the abundance and versatility of regulatory RNA, in order to emphasise the importance of these 'fine-tuners' of gene expression.

Graphical abstract. aspects of M. tuberculosis regulatory RNA discussed in this review.

Fig. 1

Riboswitch architecture. Top panel illustrates how a ligand induces transcriptional termination in a transcriptionally controlled ‘Off’ switch; panel below illustrates a translational ‘Off’ switch.

Fig. 2

Control of rpf expression in M. tuberculosis. The figure illustrates how different, sometimes shared, transcriptional regulators contribute to rpf regulation in addition to long 5’ leaders, which in the case of rpfA harbours a riboswitch with a known ligand (c-d-AMP), in rpfB a riboswitch candidate, with unknown ligand and in rpfE, a so far entirely uncharacterised element.

Fig. 3

Basic sRNA modes of action. Top half illustrates how an sRNA (cis- or trans-encoded) can block ribosome entry and translation. Bottom panel illustrates how an sRNA can activate translation by an anti-antisense mechanism; in this situation the mRNA leader itself blocks translation, by masking the TIR, but an sRNA can interact with the leader to unmask the TIR.

Fig. 4

Stability of DrrS. Large image shows the predicted structure of DrrS₁₀₈, while the schematic representation illustrates how the number of unpaired nucleotides 5’ are inversely correlated to transcript stability.

Fig. 5

The mcr7/aprABC locus in M. tuberculosis. The figure illustrates the elements associated with the PhoP/R regulated operon with the ncRNA Mcr7, which contains an open reading frame encoding the acid inducible AprA, and the proposed interaction between Mcr7 and the tatC mRNA.