Exploring the transcription start sites and other genomic features facilitates the accurate identification and annotation of small RNAs across multiple stress conditions in Mycobacterium tuberculosis.
Mycobacterium tuberculosis
/ genetics
Transcription Initiation Site
RNA, Small Untranslated
/ genetics
Operon
RNA, Bacterial
/ genetics
5' Untranslated Regions
Gene Expression Regulation, Bacterial
Stress, Physiological
/ genetics
Genome, Bacterial
3' Untranslated Regions
Molecular Sequence Annotation
Mycobacterium tuberculosis
Small regulatory RNAs
Transcription start sites
Transcriptome
Journal
Functional & integrative genomics
ISSN: 1438-7948
Titre abrégé: Funct Integr Genomics
Pays: Germany
ID NLM: 100939343
Informations de publication
Date de publication:
12 Sep 2024
12 Sep 2024
Historique:
received:
25
06
2024
accepted:
23
08
2024
revised:
22
08
2024
medline:
12
9
2024
pubmed:
12
9
2024
entrez:
12
9
2024
Statut:
epublish
Résumé
Mycobacterium tuberculosis (MTB) is a pathogen that is known for its ability to persist in harsh environments and cause chronic infections. Understanding the regulatory networks of MTB is crucial for developing effective treatments. Small regulatory RNAs (sRNAs) play important roles in gene expression regulation in all kingdoms of life, and their classification based solely on genomic location can be imprecise due to the computational-based prediction of protein-coding genes in bacteria, which often neglects segments of mRNA such as 5'UTRs, 3'UTRs, and intercistronic regions of operons. To address this issue, our study simultaneously discovered genomic features such as TSSs, UTRs, and operons together with sRNAs in the M. tuberculosis H37Rv strain (ATCC 27294) across multiple stress conditions. Our analysis identified 1,376 sRNA candidates and 8,173 TSSs in MTB, providing valuable insights into its complex regulatory landscape. TSS mapping enabled us to classify these sRNAs into more specific categories, including promoter-associated sRNAs, 5'UTR-derived sRNAs, 3'UTR-derived sRNAs, true intergenic sRNAs, and antisense sRNAs. Three of these sRNA candidates were experimentally validated using 3'-RACE-PCR: predictedRNA_0240, predictedRNA_0325, and predictedRNA_0578. Future characterization and validation are necessary to fully elucidate the functions and roles of these sRNAs in MTB. Our study is the first to simultaneously unravel TSSs and sRNAs in MTB and demonstrate that the identification of other genomic features, such as TSSs, UTRs, and operons, allows for more accurate and specific classification of sRNAs.
Identifiants
pubmed: 39264475
doi: 10.1007/s10142-024-01437-5
pii: 10.1007/s10142-024-01437-5
doi:
Substances chimiques
RNA, Small Untranslated
0
RNA, Bacterial
0
5' Untranslated Regions
0
3' Untranslated Regions
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
160Subventions
Organisme : Fundamental Research Grant Scheme
ID : 203/CIPPT/6711628
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Almagro Armenteros JJ, Tsirigos KD, Sønderby CK, Petersen TN, Winther O, Brunak S, von Heijne G, Nielsen H (2019) SignalP 5.0 improves signal peptide predictions using deep neural networks, Nat. Biotechnol. 37:420–423. https://doi.org/10.1038/s41587-019-0036-z
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410
doi: 10.1016/S0022-2836(05)80360-2
pubmed: 2231712
Andrews S (2010) FastQC: A Quality Control Tool for High Throughput Sequence Data. https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Arnvig KB, Comas I, Thomson NR, Houghton J, Boshoff HI, Croucher NJ, Rose G, Perkins TT, Parkhill J, Dougan G, Young DB (2011) Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of Mycobacterium tuberculosis. PLoS Pathog 7:e1002342. https://doi.org/10.1371/journal.ppat.1002342
doi: 10.1371/journal.ppat.1002342
pubmed: 22072964
pmcid: 3207917
Bagchi G, Chauhan S, Sharma D, Tyagi JS (2005) Transcription and autoregulation of the Rv3134c-devR-devS operon of mycobacterium tuberculosis. Microbiology 151(12):4045–4053. https://doi.org/10.1099/mic.0.28333-0
doi: 10.1099/mic.0.28333-0
pubmed: 16339949
Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37:W202–W208. https://doi.org/10.1093/nar/gkp335
doi: 10.1093/nar/gkp335
pubmed: 19458158
pmcid: 2703892
Banerjee A, Dubnau E, Quemard A, Balasubramanian V, Um KS, Wilson T, Collins D, De Lisle G, Jacobs WR (1994) inhA, a gene encoding a target for isoniazid and ethionamide in mycobacterium tuberculosis. Science 263(5144):227–230. https://doi.org/10.1126/science.8284673
doi: 10.1126/science.8284673
pubmed: 8284673
Berthet FX, Rasmussen PB, Rosenkrands I, Andersen P, Gicquel B (1998) A mycobacterium tuberculosis operon encoding ESAT-6 and a novel low-molecular-mass culture filtrate protein (CFP-10). Microbiology 144(11):3195–3203. https://doi.org/10.1099/00221287-144-11-3195
doi: 10.1099/00221287-144-11-3195
pubmed: 9846755
Bigi F, Alito A, Romano MI, Zumarraga M, Caimi K, Cataldi A (2000) The gene encoding P27 lipoprotein and a putative antibiotic-resistance gene form an operon in mycobacterium tuberculosis and Mycobacterium bovis. Microbiology 146(4):1011–1018. https://doi.org/10.1099/00221287-146-4-1011
doi: 10.1099/00221287-146-4-1011
pubmed: 10784059
Blum M, Chang H-Y, Chuguransky S, Grego T, Kandasaamy S, Mitchell A, Nuka G, Paysan-Lafosse T, Qureshi M, Raj S, Richardson L, Salazar GA, Williams L, Bork P, Bridge A, Gough J, Haft DH, Letunic I, Marchler-Bauer A, Mi H, Natale DA, Necci M, Orengo CA, Pandurangan AP, Rivoire C, Sigrist CJA, Sillitoe I, Thanki N, Thomas PD, Tosatto SCE, Wu CH, Bateman A, Finn RD (2020) The InterPro protein families and domains database: 20 years on. Nucleic Acids Res 49:D344–D354. https://doi.org/10.1093/nar/gkaa977
doi: 10.1093/nar/gkaa977
pmcid: 7778928
Brosius J (2014) The persistent contributions of RNA to eukaryotic Gen(om)e architecture and cellular function. Cold Spring Harb Perspect Biol 6:a016089. https://doi.org/10.1101/cshperspect.a016089
doi: 10.1101/cshperspect.a016089
pubmed: 25081515
pmcid: 4292154
Brosius J, Raabe CA (2016) What is an RNA? A Top Layer for RNA Classification. RNA Biol 13:140–144. https://doi.org/10.1080/15476286.2015.1128064
doi: 10.1080/15476286.2015.1128064
pubmed: 26818079
pmcid: 4829331
Brosius J, Tiedge H (2004) RNomenclature. RNA Biol 1:81–83. https://doi.org/10.4161/rna.1.2.1228
doi: 10.4161/rna.1.2.1228
pubmed: 17179746
Callen BP, Shearwin KE, Egan JB (2004) Transcriptional interference between convergent promoters caused by elongation over the promoter. Mol Cell 14:647–656. https://doi.org/10.1016/j.molcel.2004.05.010
doi: 10.1016/j.molcel.2004.05.010
pubmed: 15175159
Casali N, White AM, Riley LW (2006) Regulation of the mycobacterium tuberculosis mce1 operon. J Bacteriol 188(2):441–449. https://doi.org/10.1128/JB.188.2.441-449.2006
doi: 10.1128/JB.188.2.441-449.2006
pubmed: 16385033
pmcid: 1347267
Chao Y, Vogel J (2016) A 3’UTR-derived small RNA provides the regulatory noncoding arm of the inner membrane stress response. Mol Cell 61:352–363. https://doi.org/10.1016/j.molcel.2015.12.023
doi: 10.1016/j.molcel.2015.12.023
pubmed: 26805574
Chao Y, Papenfort K, Reinhardt R, Sharma CM, Vogel J (2012) An atlas of Hfq-bound transcripts reveals 3′ UTRs as a genomic reservoir of regulatory small RNAs: Hfq-dependent small RNAs from 3′ UTRs. EMBO J 31:4005–4019. https://doi.org/10.1038/emboj.2012.229
doi: 10.1038/emboj.2012.229
pubmed: 22922465
pmcid: 3474919
Chauhan R, Ravi J, Datta P, Chen T, Schnappinger D, Bassler KE, Balázsi G, Gennaro ML (2016) Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis. Nat Commun 7:1–12. https://doi.org/10.1038/ncomms11062
doi: 10.1038/ncomms11062
Cheah H-L, Raabe CA, Lee L-P, Rozhdestvensky TS, Citartan M, Ahmed SA, Tang T-H (2018) Bacterial regulatory RNAs: complexity, function, and putative drug targeting. Crit Rev Biochem Mol Biol 53:335–355. https://doi.org/10.1080/10409238.2018.1473330
doi: 10.1080/10409238.2018.1473330
pubmed: 29793351
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 M-A, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544. https://doi.org/10.1038/31159
doi: 10.1038/31159
pubmed: 9634230
Cortes T, Schubert OT, Rose G, Arnvig KB, Comas I, Aebersold R, Young DB (2013) Genome-wide mapping of transcriptional start sites defines an extensive leaderless transcriptome in Mycobacterium tuberculosis. Cell Rep 5:1121–1131. https://doi.org/10.1016/j.celrep.2013.10.031
doi: 10.1016/j.celrep.2013.10.031
pubmed: 24268774
pmcid: 3898074
Dar D, Sorek (2018) Extensive reshaping of bacterial operons by programmed mRNA decay, PLoS Genet. 14. https://doi.org/10.1371/journal.pgen.1007354
Desgranges E, Caldelari I, Marzi S, Lalaouna D (2020). Navigation through the twists and turns of RNA sequencing technologies: Application to bacterial regulatory RNAs. Biochimica et Biophysica Acta (BBA) - Gene Regul Mech 1863(3), 194506. https://doi.org/10.1016/j.bbagrm.2020.194506
Dugar G, Herbig A, Förstner KU, Heidrich N, Reinhardt R, Nieselt K, Sharma CM (2013) High-resolution transcriptome maps reveal strain-specific regulatory features of multiple Campylobacter jejuni isolates, PLoS Genet. 9. https://doi.org/10.1371/journal.pgen.1003495
Ewels P, Magnusson M, Lundin S, Käller M (2016) MultiQC: Summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32:3047–3048. https://doi.org/10.1093/bioinformatics/btw354
doi: 10.1093/bioinformatics/btw354
pubmed: 27312411
pmcid: 5039924
Förstner KU, Vogel J, Sharma CM (2014) READemption-a tool for the computational analysis of deep-sequencing-based transcriptome data. Bioinforma Oxf Engl 30:3421–3423. https://doi.org/10.1093/bioinformatics/btu533
doi: 10.1093/bioinformatics/btu533
Ganapathy U, Marrero J, Calhoun S, Eoh H, de Carvalho LPS, Rhee K, Ehrt S (2015) Two enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis. Nat Commun 6(1):7912. https://doi.org/10.1038/ncomms8912
doi: 10.1038/ncomms8912
pubmed: 26258286
pmcid: 4535450
Gao LY, Pak M, Kish R, Kajihara K, Brown EJ (2006) A mycobacterial operon essential for virulence in vivo and invasion and intracellular persistence in macrophages. Infect Immun 74(3):1757–1767. https://doi.org/10.1128/IAI.74.3.1757-1767.2006
doi: 10.1128/IAI.74.3.1757-1767.2006
pubmed: 16495549
pmcid: 1418628
Gardner PP, Barquist L, Bateman A, Nawrocki EP, Weinberg Z (2011) RNIE: Genome-wide prediction of bacterial intrinsic terminators. Nucleic Acids Res 39:5845–5852. https://doi.org/10.1093/nar/gkr168
doi: 10.1093/nar/gkr168
pubmed: 21478170
pmcid: 3152330
Geiman DE, Raghunand TR, Agarwal N, Bishai WR (2006) Differential gene expression in response to exposure to antimycobacterial agents and other stress conditions among seven Mycobacterium tuberculosis whiB-like genes. Antimicrob Agents Chemother 50:2836–2841. https://doi.org/10.1128/AAC.00295-06
doi: 10.1128/AAC.00295-06
pubmed: 16870781
pmcid: 1538666
Georg J, Hess WR (2011) Regulatory RNAs in cyanobacteria: developmental decisions, stress responses and a plethora of chromosomally encoded cis-antisense RNAs. Biol Chem 392:291–297. https://doi.org/10.1515/BC.2011.046
doi: 10.1515/BC.2011.046
pubmed: 21294678
Goude R, Amin AG, Chatterjee D, Parish T (2008) The critical role of embC in mycobacterium tuberculosis. J Bacteriol 190(12):4335–4341. https://doi.org/10.1128/JB.01825-07
doi: 10.1128/JB.01825-07
pubmed: 18424526
pmcid: 2446762
Güell M, Van Noort V, Yus E, Chen WH, Leigh-Bell J, Michalodimitrakis K, Yamada T, Arumugam M, Doerks T, Kühner S, Rode M, Suyama M, Schmidt S, Gavin AC, Bork P, Serrano L (2009) Transcriptome complexity in a genome-reduced bacterium. Science 326:1268–1271. https://doi.org/10.1126/science.1176951
doi: 10.1126/science.1176951
pubmed: 19965477
Güell M, Yus E, Lluch-Senar M, Serrano L (2011) Bacterial transcriptomics: What is beyond the RNA horiz-ome? Nat Rev Microbiol 9:658–669. https://doi.org/10.1038/nrmicro2620
doi: 10.1038/nrmicro2620
pubmed: 21836626
Guo MS, Updegrove TB, Gogol EB, Shabalina SA, Gross CA, Storz G (2014) MicL, a new σ
doi: 10.1101/gad.243485.114
pubmed: 25030700
pmcid: 4102768
Haning K, Cho SH, Contreras LM (2014). Small RNAs in mycobacteria: An unfolding story. Front Cell Infect Microbiol 4. https://doi.org/10.3389/fcimb.2014.00096
Hemm MR, Weaver J, Storz G (2020) Escherichia coli Small Proteome, EcoSal Plus. 9. https://doi.org/10.1128/ecosalplus.esp-0031-2019
Jackowiak P, Nowacka M, Strozycki PM, Figlerowicz M (2011) RNA degradome-its biogenesis and functions. Nucleic Acids Res 39:7361–7370. https://doi.org/10.1093/nar/gkr450
doi: 10.1093/nar/gkr450
pubmed: 21653558
pmcid: 3177198
Karls RK, Guarner J, McMurray DN, Birkness KA, Quinn FD (2006) Examination of Mycobacterium tuberculosis sigma factor mutants using low-dose aerosol infection of guinea pigs suggests a role for SigC in pathogenesis. Microbiology 152:1591–1600. https://doi.org/10.1099/mic.0.28591-0
doi: 10.1099/mic.0.28591-0
pubmed: 16735723
Kawano M, Aravind L, Storz G (2007) An antisense RNA controls synthesis of an SOS-induced toxin evolved from an antitoxin. Mol Microbiol 64:738–754. https://doi.org/10.1111/j.1365-2958.2007.05688.x
doi: 10.1111/j.1365-2958.2007.05688.x
pubmed: 17462020
pmcid: 1891008
Kerpedjiev P, Hammer S, Hofacker IL (2015) Forna (force-directed RNA): Simple and effective online RNA secondary structure diagrams. Bioinformatics 31:3377–3379. https://doi.org/10.1093/bioinformatics/btv372
doi: 10.1093/bioinformatics/btv372
pubmed: 26099263
pmcid: 4595900
Kery MB, Feldman M, Livny J, Tjaden B (2014) TargetRNA2: identifying targets of small regulatory RNAs in bacteria. Nucleic Acids Res 42:W124–W129. https://doi.org/10.1093/nar/gku317
doi: 10.1093/nar/gku317
pubmed: 24753424
pmcid: 4086111
Kieser KJ, Rubin EJ (2014) How sisters grow apart: Mycobacterial growth and division. Nat Rev Microbiol 12:550–562. https://doi.org/10.1038/nrmicro3299
doi: 10.1038/nrmicro3299
pubmed: 24998739
pmcid: 6556109
Kingsford CL, Ayanbule K, Salzberg SL (2007) Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake. Genome Biol 8:R22. https://doi.org/10.1186/gb-2007-8-2-r22.10.1016/S0022-2836(05)80360-2
doi: 10.1186/gb-2007-8-2-r22.10.1016/S0022-2836(05)80360-2
pubmed: 17313685
pmcid: 1852404
Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9:357–359. https://doi.org/10.1038/nmeth.1923
doi: 10.1038/nmeth.1923
pubmed: 22388286
pmcid: 3322381
Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG, Clustal W, Clustal X (2007) version 2.0. Bioinformatics 23:2947–2948. https://doi.org/10.1093/bioinformatics/btm404
doi: 10.1093/bioinformatics/btm404
pubmed: 17846036
Lavollay M, Arthur M, Fourgeaud M, Dubost L, Marie A, Veziris N, Blanot D, Gutmann L, Mainardi J-L (2008) The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by l, d-transpeptidation. J Bacteriol. https://doi.org/10.1128/JB.00239-08
doi: 10.1128/JB.00239-08
pubmed: 18408028
pmcid: 2446752
Li X, Mei H, Chen F, Tang Q, Yu Z, Cao X, Andongma BT, Chou SH, He J (2017) Transcriptome landscape of Mycobacterium smegmatis. Front Microbiol 8:2505. https://doi.org/10.3389/fmicb.2017.02505
doi: 10.3389/fmicb.2017.02505
pubmed: 29326668
pmcid: 5741613
Livny J, Waldor MK (2007) Identification of small RNAs in diverse bacterial species. Curr Opin Microbiol 10:96–101. https://doi.org/10.1016/j.mib.2007.03.005
doi: 10.1016/j.mib.2007.03.005
pubmed: 17383222
Lloréns-Rico V,Cano J, Kamminga T, Gil R, Latorre A, Chen WH, Bork P, Glass JI, Serrano L, Lluch-Senar M (2016) Bacterial antisense RNAs are mainly the product of transcriptional noise Sci. Adv. 2. https://doi.org/10.1126/sciadv.1501363
Loh E, Dussurget O, Gripenland J, Vaitkevicius K, Tiensuu T, Mandin P, Repoila F, Buchrieser C, Cossart P, Johansson J (2009) A trans-acting riboswitch controls expression of the virulence regulator prfA in Listeria monocytogenes. Cell 139:770–779. https://doi.org/10.1016/j.cell.2009.08.046
doi: 10.1016/j.cell.2009.08.046
pubmed: 19914169
Lorenz R, Bernhart SH, Höner Zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL (2011) ViennaRNA Package 2.0., Algorithms Mol Biol. AMB. 6: 26. https://doi.org/10.1186/1748-7188-6-26 .
Manganelli R (2014), Sigma factors: key molecules in Mycobacterium tuberculosis physiology and virulence, Microbiol. Spectr. 2: MGM2–0007–2013. https://doi.org/10.1128/microbiolspec.mgm2-0007-2013 .
Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17: 10. https://doi.org/10.14806/ej.17.1.200
McCarthy DJ, Chen Y, Smyth GK (2012) Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res 40(10):4288–4297. https://doi.org/10.1093/nar/gks042
doi: 10.1093/nar/gks042
pubmed: 22287627
pmcid: 3378882
McClure R, Balasubramanian D, Sun Y, Bobrovskyy M, Sumby P, Genco CA, Vanderpool CK, Tjaden B (2013) Computational analysis of bacterial RNA-Seq data. Nucleic Acids Res 41:e140–e140. https://doi.org/10.1093/nar/gkt444
doi: 10.1093/nar/gkt444
pubmed: 23716638
pmcid: 3737546
Milano A, Branzoni M, Canneva F, Profumo A, Riccardi G (2004) The mycobacterium tuberculosis Rv2358-furB operon is induced by zinc. Res Microbiol 155(3):192–200. https://doi.org/10.1016/j.resmic.2003.11.009
doi: 10.1016/j.resmic.2003.11.009
pubmed: 15059632
Miotto P, Forti F, Ambrosi A, Pellin D, Veiga DF, Balazsi G, Gennaro ML, Di Serio C, Ghisotti D, Cirillo DM (2012) Genome-wide discovery of small RNAs in Mycobacterium tuberculosis. PLoS ONE 7:e51950. https://doi.org/10.1371/journal.pone.0051950
doi: 10.1371/journal.pone.0051950
pubmed: 23284830
pmcid: 3526491
Miyakoshi M, Chao Y, Vogel J (2015) Regulatory small RNAs from the 3′ regions of bacterial mRNAs. Curr Opin Microbiol 24:132–139. https://doi.org/10.1016/j.mib.2015.01.013
doi: 10.1016/j.mib.2015.01.013
pubmed: 25677420
Moll I, Engelberg-Kulka H (2012) Selective translation during stress in Escherichia coli. Trends Biochem Sci 37(11):493–498. https://doi.org/10.1016/j.tibs.2012.07.007
doi: 10.1016/j.tibs.2012.07.007
pubmed: 22939840
pmcid: 4894542
Namouchi A, Gómez-Muñoz M, Frye SA, Moen LV, Rognes T, Tønjum T, Balasingham SV (2016) The Mycobacterium tuberculosis transcriptional landscape under genotoxic stress, BMC Genomics. 17. https://doi.org/10.1186/s12864-016-3132-1
Nawrocki EP, Burge SW, Bateman A, Daub J, Eberhardt RY, Eddy SR, Floden EW, Gardner PP, Jones TA, Tate J, Finn RD (2015) Rfam 12.0: Updates to the RNA families database. Nucleic Acids Res. 43:D130–D137. https://doi.org/10.1093/nar/gku1063
doi: 10.1093/nar/gku1063
pubmed: 25392425
Nguyen TG, Vargas-Blanco DA, Roberts LA, Shell SS (2020) The impact of leadered and leaderless gene structures on translation efficiency, transcript stability, and predicted transcription rates in Mycobacterium smegmatis. J Bacteriol 202(9). https://doi.org/10.1128/JB.00746-19
Okonechnikov K, Conesa A, García-Alcalde F (2016) Qualimap 2: Advanced multi-sample quality control for high-throughput sequencing data. Bioinformatics 32(2):292–294. https://doi.org/10.1093/bioinformatics/btv566
doi: 10.1093/bioinformatics/btv566
pubmed: 26428292
Ollinger J, O’Malley T, Ahn J, Odingo J, Parish T (2012) Inhibition of the sole type i signal peptidase of Mycobacterium tuberculosis is bactericidal under replicating and nonreplicating conditions. J Bacteriol. https://journals.asm.org/doi/abs/ https://doi.org/10.1128/JB.00224-12 (accessed December 20, 2021)
Orr MW, Mao Y, Storz G, Qian S-B (2019) Alternative ORFs and small ORFs: shedding light on the dark proteome. Nucleic Acids Res 48:1029–1042. https://doi.org/10.1093/nar/gkz734
doi: 10.1093/nar/gkz734
pmcid: 7026640
Osbourn AE, Field B (2009) Operons. Cell Mol Life Sci 66:3755–3775. https://doi.org/10.1007/s00018-009-0114-3
doi: 10.1007/s00018-009-0114-3
pubmed: 19662496
pmcid: 2776167
Österberg S, del Peso-Santos T, Shingler V (2011) Regulation of Alternative Sigma Factor Use. Annu Rev Microbiol 65:37–55. https://doi.org/10.1146/annurev.micro.112408.134219
doi: 10.1146/annurev.micro.112408.134219
pubmed: 21639785
Otto C, Stadler PF, Hoffmann S (2014) Lacking alignments? The next-Generation Sequencing Mapper Segemehl Revisited. Bioinformatics 30:1837–1843. https://doi.org/10.1093/bioinformatics/btu146
doi: 10.1093/bioinformatics/btu146
pubmed: 24626854
Palmer AC, Barry Egan J, Shearwin KE (2011) Transcriptional interference by RNA polymerase pausing and dislodgement of transcription factors Transcription. 2:9–14. https://doi.org/10.4161/trns.2.1.13511 .
Papenfort K, Vogel J (2010) Regulatory RNA in bacterial pathogens. Cell Host Microbe 8:116–127. https://doi.org/10.1016/j.chom.2010.06.008
doi: 10.1016/j.chom.2010.06.008
pubmed: 20638647
Pasca MR, Guglierame P, Arcesi F, Bellinzoni M, De Rossi E, Riccardi G (2004) Rv2686c-Rv2687c-Rv2688c, an ABC fluoroquinolone efflux pump in mycobacterium tuberculosis. Antimicrob Agents Chemother 48(8):3175–3178. https://doi.org/10.1128/AAC.48.8.3175-3178.2004
doi: 10.1128/AAC.48.8.3175-3178.2004
pubmed: 15273144
pmcid: 478549
Perkins TT, Kingsley RA, Fookes MC, Gardner PP, James KD, Yu L, Assefa SA, He M, Croucher NJ, Pickard DJ, Maskell DJ, Parkhill J, Choudhary J, Thomson NR, Dougan G (2009) A strand-specific RNA-seq analysis of the transcriptome of the typhoid bacillus Salmonella typhi. PLoS Genet 5:e1000569. https://doi.org/10.1371/journal.pgen.1000569
doi: 10.1371/journal.pgen.1000569
pubmed: 19609351
pmcid: 2704369
Quinlan AR, Hall IM (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26:841–842. https://doi.org/10.1093/bioinformatics/btq033
doi: 10.1093/bioinformatics/btq033
pubmed: 20110278
pmcid: 2832824
Raabe CA, Hoe CH, Randau G, Brosius J, Tang TH, Rozhdestvensky TS (2011) The rocks and shallows of deep RNA sequencing: Examples in the Vibrio cholerae RNome. RNA n y n 17:1357–1366. https://doi.org/10.1261/rna.2682311
doi: 10.1261/rna.2682311
Razavi M, Kristiansson E, Flach C-F, Larsson DGJ (2020) The Association between Insertion Sequences and Antibiotic Resistance Genes, MSphere. 5. https://doi.org/10.1128/msphere.00418-20
Robinson MD, McCarthy DJ, Smyth GK (2010) Edger: A bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140. https://doi.org/10.1093/bioinformatics/btp616
doi: 10.1093/bioinformatics/btp616
pubmed: 19910308
Rodriguez GM, Voskuil MI, Gold B, Schoolnik GK, Smith I (2002) ideR, an essential gene in Mycobacterium tuberculosis: Role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect Immun 70:3371–3381. https://doi.org/10.1128/IAI.70.7.3371-3381.2002
doi: 10.1128/IAI.70.7.3371-3381.2002
pubmed: 12065475
pmcid: 128082
Rosas-Magallanes V, Deschavanne P, Quintana-Murci L, Brosch R, Gicquel B, Neyrolles O (2006) Horizontal transfer of a virulence operon to the ancestor of mycobacterium tuberculosis. Mol Biol Evol 23(6):1129–1135. https://doi.org/10.1093/molbev/msj120
doi: 10.1093/molbev/msj120
pubmed: 16520338
Sass AM, Van Acker H, Förstner KU, Van Nieuwerburgh F, Deforce D, Vogel J, Coenye T (2015) Genome-wide transcription start site profiling in biofilm-grown Burkholderia cenocepacia J2315, BMC Genomics 16. https://doi.org/10.1186/s12864-015-1993-3
Shao W, Price MN, Deutschbauer AM, Romine MF, Arkin AP (2014) Conservation of transcription start sites within genes across a bacterial genus, MBio. 5 https://doi.org/10.1128/mbio.01398-14 . https://doi.org/10.1128/mbio.01398-14
Sharma CM, Hoffmann S, Darfeuille F, Reignier J, Findeiß S, Sittka A, Chabas S, Reiche K, Hackermüller J, Reinhardt R, Stadler PF, Vogel J (2010) The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464:250–255. https://doi.org/10.1038/nature08756
doi: 10.1038/nature08756
pubmed: 20164839
Shearwin KE, Callen BP, Egan JB (2005) Transcriptional interference - A crash course. Trends Genet 21:339–345. https://doi.org/10.1016/j.tig.2005.04.009
doi: 10.1016/j.tig.2005.04.009
pubmed: 15922833
pmcid: 2941638
Shell SS, Wang J, Lapierre P, Mir M, Chase MR, Pyle MM, Gawande R, Ahmad R, Sarracino DA, Ioerger TR, Fortune SM, Derbyshire KM, Wade JT, Gray TA (2015) Leaderless Transcripts and Small Proteins Are Common Features of the Mycobacterial Translational Landscape. PLOS Genet 11:e1005641. https://doi.org/10.1371/journal.pgen.1005641
doi: 10.1371/journal.pgen.1005641
pubmed: 26536359
pmcid: 4633059
Singh A, Jain S, Gupta S, Das T, Tyagi AK (2003) mymA operon of mycobacterium tuberculosis: its regulation and importance in the cell envelope. FEMS Microbiol Lett 227(1):53–63. https://doi.org/10.1016/S0378-1097(03)00648-7
doi: 10.1016/S0378-1097(03)00648-7
pubmed: 14568148
Sittka A, Lucchini S, Papenfort K, Sharma CM, Rolle K, Binnewies TT, Hinton JCD, Vogel J (2008) Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq, PLoS Genet. 4. https://doi.org/10.1371/journal.pgen.1000163
Smith RA, Parkinson JS (1980) Overlapping genes at the cheA locus of Escherichia coli. Proc Natl Acad Sci 77:5370–5374. https://doi.org/10.1073/pnas.77.9.5370
doi: 10.1073/pnas.77.9.5370
pubmed: 6449010
pmcid: 350060
Sorek R, Cossart P (2010) Prokaryotic transcriptomics: A new view on regulation, physiology and pathogenicity. Nat Rev Genet 11:9–16. https://doi.org/10.1038/nrg2695
doi: 10.1038/nrg2695
pubmed: 19935729
Sousa ME, Farkas MH (2018) Micropeptide. PLOS Genet 14:e1007764. https://doi.org/10.1371/journal.pgen.1007764
doi: 10.1371/journal.pgen.1007764
pubmed: 30543625
pmcid: 6292567
Stermann M, Bohrssen A, Diephaus C, Maass S, Bange FC (2003) Polymorphic nucleotide within the promoter of nitrate reductase (NarGHJI) is specific for mycobacterium tuberculosis. J Clin Microbiol 41(7):3252–3259. https://doi.org/10.1128/JCM.41.7.3252-3259.2003
doi: 10.1128/JCM.41.7.3252-3259.2003
pubmed: 12843072
pmcid: 165301
Sun R, Converse PJ, Ko C, Tyagi S, Morrison NE, Bishai WR (2004) Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol Microbiol 52:25–38. https://doi.org/10.1111/j.1365-2958.2003.03958.x
doi: 10.1111/j.1365-2958.2003.03958.x
pubmed: 15049808
Supply P, Magdalena J, Himpens S, Locht C (1997) Identification of novel intergenic repetitive units in a mycobacterial two-component system operon. Mol Microbiol 26(5):991–1003. https://doi.org/10.1046/j.1365-2958.1997.6361999.x
doi: 10.1046/j.1365-2958.1997.6361999.x
pubmed: 9426136
Taneja S, Dutta T (2019) On a stake-out: Mycobacterial small RNA identification and regulation. Non-Coding RNA Research 4(3):86–95. https://doi.org/10.1016/j.ncrna.2019.05.001
doi: 10.1016/j.ncrna.2019.05.001
pubmed: 32083232
pmcid: 7017587
Thomason MK, Bischler T, Eisenbart SK, Förstner KU, Zhang A, Herbig A, Nieselt K, Sharma CM, Storza G (2015) Global transcriptional start site mapping using differential RNA sequencing reveals novel antisense RNAs in Escherichia coli. J Bacteriol 197:18–28. https://doi.org/10.1128/JB.02096-14
doi: 10.1128/JB.02096-14
pubmed: 25266388
Thorvaldsdottir H, Robinson JT, Mesirov JP (2013) Integrative Genomics Viewer (Igv): high-performance genomics data visualization and exploration. Brief Bioinform 14:178–192. https://doi.org/10.1093/bib/bbs017
doi: 10.1093/bib/bbs017
pubmed: 22517427
Tjaden B (2015) De novo assembly of bacterial transcriptomes from RNA-seq data, Genome Biol 16: https://doi.org/10.1186/s13059-014-0572-2 .
Tjaden B (2020) A computational system for identifying operons based on RNA-seq data. Methods 176:62–70. https://doi.org/10.1016/j.ymeth.2019.03.026
doi: 10.1016/j.ymeth.2019.03.026
pubmed: 30953757
Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H, Balestrino D, Loh E, Gripenland J, Tiensuu T, Vaitkevicius K, Barthelemy M, Vergassola M, Nahori MA, Soubigou G, Régnault B, Coppée JY, Lecuit M, Johansson J, Cossart P (2009) The Listeria transcriptional landscape from saprophytism to virulence. Nature 459:950–956. https://doi.org/10.1038/nature08080
doi: 10.1038/nature08080
pubmed: 19448609
Torres A, Juárez MD, Cervantes R, Espitia C (2001) Molecular analysis of mycobacterium tuberculosis phosphate specific transport system in mycobacterium smegmatis. Characterization of recombinant 38 kDa (PstS-1). Microb Pathog 30(5):289–297. https://doi.org/10.1006/mpat.2001.0434
doi: 10.1006/mpat.2001.0434
pubmed: 11373123
Tundup S, Akhter Y, Thiagarajan D, Hasnain SE (2006) Clusters of PE and PPE genes of mycobacterium tuberculosis are organized in operons: evidence that PE Rv2431c is co-transcribed with PPE Rv2430c and their gene products interact with each other. FEBS Lett 580(5):1285–1293. https://doi.org/10.1016/j.febslet.2006.01.042
doi: 10.1016/j.febslet.2006.01.042
pubmed: 16458305
Updegrove TB, Shabalina SA, Storz G (2015) How do base-pairing small RNAs evolve? FEMS Microbiol Rev 39(3):379–391. https://doi.org/10.1093/femsre/fuv014
doi: 10.1093/femsre/fuv014
pubmed: 25934120
pmcid: 4542690
Vandecraen J, Chandler M, Aertsen A, Van Houdt R (2017) The impact of insertion sequences on bacterial genome plasticity and adaptability. Crit Rev Microbiol 43:709–730. https://doi.org/10.1080/1040841x.2017.1303661
doi: 10.1080/1040841x.2017.1303661
pubmed: 28407717
Vesper O, Amitai S, Belitsky M, Byrgazov K, Kaberdina AC, Engelberg-Kulka H, Moll I (2011) Selective translation of leaderless mrnas by specialized ribosomes generated by mazf in Escherichia coli. Cell 147(1):147–157. https://doi.org/10.1016/j.cell.2011.07.047
doi: 10.1016/j.cell.2011.07.047
pubmed: 21944167
pmcid: 4894548
Wagner EGH, Romby P (2015) Small RNAs in Bacteria and Archaea: Who They Are, What They Do, and How They Do It. Adv Genet 90:133–208. https://doi.org/10.1016/bs.adgen.2015.05.001
doi: 10.1016/bs.adgen.2015.05.001
pubmed: 26296935
Wang M, Fleming J, Li Z, Li C, Zhang H, Xue Y, Chen M, Zhang Z, Zhang XE, Bi L (2016) An automated approach for global identification of sRNA-encoding regions in RNA-Seq data from Mycobacterium tuberculosis. Acta Biochim Biophys Sin 48:544–553. https://doi.org/10.1093/abbs/gmw037
doi: 10.1093/abbs/gmw037
pubmed: 27174874
pmcid: 4913526
Waters LS, Storz G (2009) Regulatory RNAs in Bacteria. Cell 136:615–628. https://doi.org/10.1016/j.cell.2009.01.043
doi: 10.1016/j.cell.2009.01.043
pubmed: 19239884
pmcid: 3132550
Watkins HA, Baker EN (2006) Structural and functional analysis of rv3214 from Mycobacterium tuberculosis, a protein with conflicting functional annotations, leads to its characterization as a phosphatase. J Bacteriol 188(10):3589–3599. https://doi.org/10.1128/JB.188.10.3589-3599.2006
doi: 10.1128/JB.188.10.3589-3599.2006
pubmed: 16672613
pmcid: 1482868
Weinberg Z, Barrick JE, Yao Z, Roth A, Kim JN, Gore J, Wang JX, Lee ER, Block KF, Sudarsan N, Neph S, Tompa M, Ruzzo WL, Breaker RR (2007) Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res 35:4809–4819. https://doi.org/10.1093/nar/gkm487
doi: 10.1093/nar/gkm487
pubmed: 17621584
pmcid: 1950547
World Health Organization, Global tuberculosis report 2021, World Health Organization, Geneva, 2021. https://apps.who.int/iris/handle/10665/346387 (accessed January 7, 2022).
Yoder-Himes DR, Chain PSG, Zhu Y, Wurtzel O, Rubin EM, Tiedje JM, Sorek R (2009) Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing. Proc Natl Acad Sci 106:3976–3981. https://doi.org/10.1073/pnas.0813403106
doi: 10.1073/pnas.0813403106
pubmed: 19234113
pmcid: 2645912
Zolotarev AS, Unnikrishnan M, Shmukler BE, Clark JS, Vandorpe DH, Grigorieff N, Rubin EJ, Alper SL (2008) Increased sulfate uptake by E. coli overexpressing the SLC26-related SulP protein Rv1739c from Mycobacterium tuberculosis. Comp Biochem Physiol A Mol Integr Physiol 149:255–266. https://doi.org/10.1016/j.cbpa.2007.12.005
doi: 10.1016/j.cbpa.2007.12.005
pubmed: 18255326