Question

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What are sRNAs and what is their role in gene regulation in general and in Mycobacterium specifically?

Answer 1

Small RNAs play a major role in the post-transcriptional regulation of gene expression. Though RNAi was initially discovered in nematodes and plants, RNA-mediated regulation is widely found in eukaryotic organisms, and similar small RNA guided regulatory pathways appear to be operative in prokaryotes. Eukaryotic small RNAs play critical roles in regulating gene expression in development, cancer biology, anti-viral defense and chromatin modification. Researchers have capitalized on regulatory pathways mediated by small RNAs to enable analyses of gene function not previously possible.

Persistence of mycobacteria in the hostile environment of human macrophage is pivotal for its successful pathogenesis. Rapid adaptation to diverse stresses is the key aspect for their survival in the host cells. A range of heterogeneous mechanisms operate in bacteria to retaliate stress conditions. Small RNAs (sRNA) have been implicated in many of those mechanisms in either a single or multiple regulatory networks to post-transcriptionally modulate bacterial gene expression. Although small RNA profiling in mycobacteria by advanced technologies like deep sequencing, tilling microarray etc. have identified hundreds of sRNA, however, a handful of those small RNAs have been unearthed with precise regulatory mechanism. Extensive investigations on sRNA-mediated gene regulations in eubacteria like E.coli revealed the existence of a plethora of distinctive sRNA mechanisms e.g. base pairing, protein sequestration, RNA decoy etc. Increasing studies on mycobacterial sRNA also discovered several eccentric mechanisms where sRNAs act at the posttranscriptional stage to either activate or repress target gene expression that lead to promote mycobacterial survival in stresses. Several intrinsic features like high GC content, absence of any homologue of abundant RNA chaperones, Hfq and ProQ, isolate sRNA mechanisms of mycobacteria from that of other bacteria. An insightful approach has been taken in this review to describe sRNA identification and its regulations in mycobacterial species especially in Mycobacterium.