Abstract
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, in culture, in infected mammalian cells, and in patients. Among these noncoding RNAs are both small RNAs (sRNAs) between 50 and 350 nts in length and smaller RNAs (sncRNA) < 50 nts. In this review, we provide an up-to-date synopsis of the identification, designation, and function of these Mtb-encoded sRNAs and sncRNAs. The methodological advances including RNA sequencing strategies, small RNA antagonists, and locked nucleic acid sequence-specific RNA probes advancing the studies on these small RNA are described. Initial insights into the regulation of the small RNA expression and putative processing enzymes required for their synthesis and function are discussed. There are many open questions remaining about the biological and pathogenic roles of these small non-coding RNAs, and potential research directions needed to define the role of these mycobacterial noncoding RNAs are summarized.
Highlights
Mycobacterium tuberculosis (Mtb) remains one of the leading infectious causes of human mortality, supplanted only in 2020 by the COVID-19 pandemic triggered by the SARSCoV-2 virus
Mtb-encoded small RNAs are emerging as new regulators of mycobacterial growth, survival, and pathogenesis
LNA power inhibitors recently validated on smaller noncoding RNAs (sncRNAs)-1 are a very tractable system for blocking small RNAs (sRNAs) functions [13]
Summary
Mycobacterium tuberculosis (Mtb) remains one of the leading infectious causes of human mortality, supplanted only in 2020 by the COVID-19 pandemic triggered by the SARSCoV-2 virus. Mtb evolved from an ancestral smooth tubercule bacillus (e.g., M. canettii, M. pseudotuberculosis), acquiring virulence elements to attain its preferred pathogenicity towards humans [1]. The acquisition of these virulence elements coincided with Mtb undergoing a genomic downsizing relative to the 100 different smooth tubercule bacilli species characterized [1,2]. Despite this downsizing, a core genome is evident among the pathogenic strains of mycobacteria. Recent discoveries pertaining to these sRNAs are described Emerging reports detailing their diverse functions along with their transcriptional regulation and processing are discussed. Future directions of research and therapeutic strategies to manipulate such sRNAs are presented
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