Mycobacterium tuberculosis sRNA explained

Mycobacterium tuberculosis contains at least nine small RNA families in its genome.^[1] The small RNA (sRNA) families were identified through RNomics – the direct analysis of RNA molecules isolated from cultures of Mycobacterium tuberculosis.^{[2] [3]} The sRNAs were characterised through RACE mapping and Northern blot experiments. Secondary structures of the sRNAs were predicted using Mfold.^[4]

sRNAPredict2 – a bioinformatics tool – suggested 56 putative sRNAs in M. tuberculosis, though these have yet to be verified experimentally.^[5] Hfq protein homologues have yet to be found in M. tuberculosis;^[6] an alternative pathway – potentially involving conserved C-rich motifs – has been theorised to enable trans-acting sRNA functionality.

sRNAs were shown to have important physiological roles in M. tuberculosis. Overexpression of G2 sRNA, for example, prevented growth of M. tuberculosis and greatly reduced the growth of M. smegmatis; ASdes sRNA is thought to be a cis-acting regulator of a fatty acid desaturase (desA2) while ASpks is found with the open reading frame for Polyketide synthase-12 (pks12) and is an antisense regulator of pks12 mRNA.

The sRNA ncrMT1302 was found to be flanked by the MT1302 and MT1303 open reading frames. MT1302 encodes an adenylyl cyclase that converts ATP to cAMP, the expression of ncrMT1302 is regulated by cAMP and pH.^[7]

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.^[8]

npcTB_6715 is a first sRNA identified as a potential biomarker for the detection of MTB in patients.^[9]

See also

• Bacillus subtilis sRNAs
• Bacterial small RNA
• Brucella sRNA
• Bacteroides thetaiotaomicron sRNA
• Caenorhabditis elegans sRNA
• Escherichia coli sRNA
• Pseudomonaa sRNA

Further reading

• Pánek J, Bobek J, Mikulík K, Basler M, Vohradský J . Biocomputational prediction of small non-coding RNAs in Streptomyces . BMC Genomics . 9 . 217 . May 2008 . 18477385 . 2422843 . 10.1186/1471-2164-9-217 . free .
• Livny J, Waldor MK . Identification of small RNAs in diverse bacterial species . Current Opinion in Microbiology . 10 . 2 . 96–101 . April 2007 . 17383222 . 10.1016/j.mib.2007.03.005 .
• Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, Barry CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream MA, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG . 6 . Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence . Nature . 393 . 6685 . 537–544 . June 1998 . 9634230 . 10.1038/31159 . 1998Natur.393..537C . free .
• Arnvig KB, Gopal B, Papavinasasundaram KG, Cox RA, Colston MJ . The mechanism of upstream activation in the rrnB operon of Mycobacterium smegmatis is different from the Escherichia coli paradigm . Microbiology . 151 . Pt 2 . 467–473 . February 2005 . 15699196 . 10.1099/mic.0.27597-0 . free .
• Matsunaga I, Bhatt A, Young DC, Cheng TY, Eyles SJ, Besra GS, Briken V, Porcelli SA, Costello CE, Jacobs WR, Moody DB . Mycobacterium tuberculosis pks12 produces a novel polyketide presented by CD1c to T cells . The Journal of Experimental Medicine . 200 . 12 . 1559–1569 . December 2004 . 15611286 . 2211992 . 10.1084/jem.20041429 .

Notes and References

1. Arnvig KB, Young DB . Identification of small RNAs in Mycobacterium tuberculosis . Molecular Microbiology . 73 . 3 . 397–408 . August 2009 . 19555452 . 2764107 . 10.1111/j.1365-2958.2009.06777.x .
2. Vogel J, Bartels V, Tang TH, Churakov G, Slagter-Jäger JG, Hüttenhofer A, Wagner EG . RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria . Nucleic Acids Research . 31 . 22 . 6435–6443 . November 2003 . 14602901 . 275561 . 10.1093/nar/gkg867 .
3. Kawano M, Reynolds AA, Miranda-Rios J, Storz G . Detection of 5′- and 3′-UTR-derived small RNAs and cis-encoded antisense RNAs in Escherichia coli . Nucleic Acids Research . 33 . 3 . 1040–1050 . 2005 . 15718303 . 549416 . 10.1093/nar/gki256 .
4. Zuker M . Mfold web server for nucleic acid folding and hybridization prediction . Nucleic Acids Research . 31 . 13 . 3406–3415 . July 2003 . 12824337 . 169194 . 10.1093/nar/gkg595 .
5. Livny J, Brencic A, Lory S, Waldor MK . Identification of 17 Pseudomonas aeruginosa sRNAs and prediction of sRNA-encoding genes in 10 diverse pathogens using the bioinformatic tool sRNAPredict2 . Nucleic Acids Research . 34 . 12 . 3484–3493 . 2006 . 16870723 . 1524904 . 10.1093/nar/gkl453 .
6. Sun X, Zhulin I, Wartell RM . Predicted structure and phyletic distribution of the RNA-binding protein Hfq . Nucleic Acids Research . 30 . 17 . 3662–3671 . September 2002 . 12202750 . 137430 . 10.1093/nar/gkf508 .
7. Pelly S, Bishai WR, Lamichhane G . A screen for non-coding RNA in Mycobacterium tuberculosis reveals a cAMP-responsive RNA that is expressed during infection . Gene . 500 . 1 . 85–92 . May 2012 . 22446041 . 3340464 . 10.1016/j.gene.2012.03.044 .
8. Solans L, Gonzalo-Asensio J, Sala C, Benjak A, Uplekar S, Rougemont J, Guilhot C, Malaga W, Martín C, Cole ST . The PhoP-dependent ncRNA Mcr7 modulates the TAT secretion system in Mycobacterium tuberculosis . PLOS Pathogens . 10 . 5 . e1004183 . May 2014 . 24874799 . 4038636 . 10.1371/journal.ppat.1004183 . free .
9. Kanniappan P, Ahmed SA, Rajasekaram G, Marimuthu C, Ch'ng ES, Lee LP, Raabe CA, Rozhdestvensky TS, Tang TH . RNomic identification and evaluation of npcTB_6715, a non-protein-coding RNA gene as a potential biomarker for the detection of Mycobacterium tuberculosis . Journal of Cellular and Molecular Medicine . 21 . 10 . 2276–2283 . October 2017 . 28756649 . 5618688 . 10.1111/jcmm.13148 .