Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

'' contains at least nine

small RNA Small RNA (sRNA) are polymeric RNA molecules that are less than 200 nucleotides in length, and are usually non-coding Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA ...

families in its

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

. The small RNA (sRNA) families were identified through RNomics – the direct analysis of RNA molecules isolated from

cultures Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these groups.Tyl ...

of ''Mycobacterium tuberculosis''. The sRNAs were characterised through RACE mapping and

Northern blot The northern blot, or RNA blot,Gilbert, S. F. (2000) Developmental Biology, 6th Ed. Sunderland MA, Sinauer Associates. is a technique used in molecular biology research to study gene expression by detection of RNA (or isolated mRNA) in a sample.K ...

experiments.

Secondary structure Protein secondary structure is the three dimensional conformational isomerism, form of ''local segments'' of proteins. The two most common Protein structure#Secondary structure, secondary structural elements are alpha helix, alpha helices and beta ...

s of the sRNAs were predicted using Mfold. sRNAPredict2 – a

bioinformatics Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

tool – suggested 56 putative sRNAs in ''M. tuberculosis'', though these have yet to be verified experimentally.

Hfq protein The Hfq protein (also known as HF-I protein) encoded by the ''hfq'' gene was discovered in 1968 as an ''Escherichia coli'' host factor that was essential for replication of the bacteriophage Qβ. It is now clear that Hfq is an abundant bacterial R ...

homologues have yet to be found in ''M. tuberculosis''; an alternative pathway – potentially involving conserved C-rich motifs – has been theorised to enable

trans-acting In the field of molecular biology, ''trans''-acting (''trans''-regulatory, ''trans''-regulation), in general, means "acting from a different molecule" (''i.e.'', intermolecular). It may be considered the opposite of ''cis''-acting (''cis''-regulat ...

sRNA functionality. sRNAs were shown to have important

physiological Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

roles in ''M. tuberculosis''. Overexpression of G2 sRNA, for example, prevented growth of ''M. tuberculosis'' and greatly reduced the growth of ''

M. smegmatis ''Mycobacterium smegmatis'' is an acid-fast bacterium, bacterial species in the phylum ''Actinomycetota'' and the genus ''Mycobacterium''. It is 3.0 to 5.0 µm long with a bacillus (shape), bacillus shape and can be stained by Ziehl–Neels ...

''; ASdes sRNA is thought to be a

cis-acting ''Cis''-regulatory elements (CREs) or ''Cis''-regulatory modules (CRMs) are regions of non-coding DNA which regulate the transcription of neighboring genes. CREs are vital components of genetic regulatory networks, which in turn control morpho ...

regulator of a

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...

desaturase (desA2) while ASpks is found with the

open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...

for

Polyketide synthase Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

-12 (''pks12'') and is an antisense regulator of ''pks12''

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

. The sRNA ncrMT1302 was found to be flanked by the MT1302 and MT1303

open reading frames In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...

. MT1302 encodes an

adenylyl cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

that converts ATP to

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

, the expression of ncrMT1302 is regulated by cAMP and pH. Mcr7 sRNA encoded by the ''mcr7'' gene modulates translation of the mRNA and impacts the activity of the Twin Arginine Translocation (Tat) protein secretion apparatus. npcTB_6715 is a first sRNA identified as a potential biomarker for the detection of MTB in patients.

See also

References

Further reading