Sequence-Based Analysis Uncovers an Abundance of Non-Coding RNA in the Total Transcriptome of
RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA, including long 5’ and 3’ untranslated regions, antisense transcripts, and intergenic small RNA (sRNA) molecules. More than a quarter of all sequence reads mapping outside of ribosomal RNA genes represent non-coding RNA, and the density of reads mapping to intergenic regions was more than two-fold higher than that mapping to annotated coding sequences. Selected sRNAs were found at increased abundance in stationary phase cultures and accumulated to remarkably high levels in the lungs of chronically infected mice, indicating a potential contribution to pathogenesis. The ability of tubercle bacilli to adapt to changing environments within the host is critical to their ability to cause disease and to persist during drug treatment; it is likely that novel post-transcriptional regulatory networks will play an important role in these adaptive responses.
Vyšlo v časopise:
Sequence-Based Analysis Uncovers an Abundance of Non-Coding RNA in the Total Transcriptome of. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002342
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002342
Souhrn
RNA sequencing provides a new perspective on the genome of Mycobacterium tuberculosis by revealing an extensive presence of non-coding RNA, including long 5’ and 3’ untranslated regions, antisense transcripts, and intergenic small RNA (sRNA) molecules. More than a quarter of all sequence reads mapping outside of ribosomal RNA genes represent non-coding RNA, and the density of reads mapping to intergenic regions was more than two-fold higher than that mapping to annotated coding sequences. Selected sRNAs were found at increased abundance in stationary phase cultures and accumulated to remarkably high levels in the lungs of chronically infected mice, indicating a potential contribution to pathogenesis. The ability of tubercle bacilli to adapt to changing environments within the host is critical to their ability to cause disease and to persist during drug treatment; it is likely that novel post-transcriptional regulatory networks will play an important role in these adaptive responses.
Zdroje
1. WHO 2009 Global tuberculosis control - epidemiology, strategy, financing. Geneva WHO
2. BarryCE3rdBoshoffHIDartoisVDickTEhrtS 2009 The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat Rev Microbiol 7 845 855
3. ReddyTBRileyRWymoreFMontgomeryPDeCaprioD 2009 TB database: an integrated platform for tuberculosis research. Nucleic Acids Res 37 D499 508
4. ManganelliRVoskuilMI Schoolnik GK, Dubnau E, Gomez M, et al. 2002 Role of the extracytoplasmic-function sigma factor sigma(H) in Mycobacterium tuberculosis global gene expression. Mol Microbiol 45 365 374
5. ParkHDGuinnKMHarrellMILiaoRVoskuilMI 2003 Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol Microbiol 48 833 843
6. RustadTRHarrellMILiaoRShermanDR 2008 The enduring hypoxic response of Mycobacterium tuberculosis. PLoS One 3 e1502
7. SchnappingerDEhrtSVoskuilMILiuYManganJA 2003 Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. J Exp Med 198 693 704
8. VoskuilMISchnappingerDViscontiKCHarrellMIDolganovGM 2003 Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J Exp Med 198 705 713
9. WaltersSBDubnauEKolesnikovaILavalFDaffeM 2006 The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol Microbiol 60 312 330
10. ColeSTBroschRParkhillJGarnierTChurcherC 1998 Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393 537 544
11. GripenlandJNetterlingSLohETiensuuTToledo-AranaA 2010 RNAs: regulators of bacterial virulence. Nat Rev Microbiol 8 857 866
12. PapenfortKVogelJ 2010 Regulatory RNA in bacterial pathogens. Cell Host Microbe 8 116 127
13. WatersLSStorzG 2009 Regulatory RNAs in bacteria. Cell 136 615 628
14. MandalMBreakerRR 2004 Gene regulation by riboswitches. Nat Rev Mol Cell Biol 5 451 463
15. LohEDussurgetOGripenlandJVaitkeviciusKTiensuuT 2009 A trans-acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 139 770 779
16. GottesmanSStorzG 2010 Bacterial Small RNA Regulators: Versatile Roles and Rapidly Evolving Variations. Cold Spring Harb Perspect Biol Epub ahead of print. pii doi:10.1101/cshperspect.a003798 cshperspect.a003798v1
17. Toledo-AranaADussurgetONikitasGSestoNGuet-RevilletH 2009 The Listeria transcriptional landscape from saprophytism to virulence. Nature 459 950 956
18. PfeifferVSittkaATomerRTedinKBrinkmannV 2007 A small non-coding RNA of the invasion gene island (SPI-1) represses outer membrane protein synthesis from the Salmonella core genome. Mol Microbiol 66 1174 1191
19. PichonCFeldenB 2005 Small RNA genes expressed from Staphylococcus aureus genomic and pathogenicity islands with specific expression among pathogenic strains. Proc Natl Acad Sci U S A 102 14249 14254
20. MandinPRepoilaFVergassolaMGeissmannTCossartP 2007 Identification of new noncoding RNAs in Listeria monocytogenes and prediction of mRNA targets. Nucleic Acids Res 35 962 974
21. ArnvigKBYoungDB 2010 Regulation of pathogen metabolism by small RNA. Drug Discov Today Dis Mech 7 e19 e24
22. ArnvigKBYoungDB 2009 Identification of small RNAs in Mycobacterium tuberculosis. Mol Microbiol 73 397 408
23. DichiaraJMContreras-MartinezLMLivnyJSmithDMcDonoughKA 2010 Multiple small RNAs identified in Mycobacterium bovis BCG are also expressed in Mycobacterium tuberculosis and Mycobacterium smegmatis. Nucleic Acids Res 38 4067 78
24. PerkinsTTKingsleyRAFookesMCGardnerPPJamesKD 2009 A strand-specific RNA-Seq analysis of the transcriptome of the typhoid bacillus Salmonella typhi. PLoS Genet 5 e1000569
25. SharmaCMHoffmannSDarfeuilleFReignierJFindeissS 2010 The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464 250 255
26. SittkaALucchiniSPapenfortKSharmaCMRolleK 2008 Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator, Hfq. PLoS Genet 4 e1000163
27. AlbrechtMSharmaCMReinhardtRVogelJRudelT 2010 Deep sequencing-based discovery of the Chlamydia trachomatis transcriptome. Nucleic Acids Res 38 868 877
28. BohnCRigoulayCChabelskayaSSharmaCMMarchaisA 2010 Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism. Nucleic Acids Res 38 6620 6636
29. GuellMvan NoortVYusEChenWHLeigh-BellJ 2009 Transcriptome complexity in a genome-reduced bacterium. Science 326 1268 1271
30. BitterWHoubenENLuirinkJAppelmelkBJ 2009 Type VII secretion in mycobacteria: classification in line with cell envelope structure. Trends Microbiol 17 337 338
31. PymASBrodinPBroschRHuerreMColeST 2002 Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti. Mol Microbiol 46 709 717
32. SkjotRLOettingerTRosenkrandsIRavnPBrockI 2000 Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens. Infect Immun 68 214 220
33. RamageHRConnollyLECoxJS 2009 Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet 5 e1000767
34. RustadTRSherridAMMinchKJShermanDR 2009 Hypoxia: a window into Mycobacterium tuberculosis latency. Cell Microbiol 11 1151 1159
35. RutherfordKParkhillJCrookJHorsnellTRiceP 2000 Artemis: sequence visualization and annotation. Bioinformatics 16 944 945
36. SorekRKuninVHugenholtzP 2008 CRISPR--a widespread system that provides acquired resistance against phages in bacteria and archaea. Nat Rev Microbiol 6 181 186
37. KarginovFVHannonGJ 2010 The CRISPR system: small RNA-guided defense in bacteria and archaea. Mol Cell 37 7 19
38. GardnerPPDaubJTateJGNawrockiEPKolbeDL 2009 Rfam: updates to the RNA families database. Nucleic Acids Res 37 D136 140
39. StewartGRWernischLStablerRManganJAHindsJ 2002 Dissection of the heat-shock response in Mycobacterium tuberculosis using mutants and microarrays. Microbiology 148 3129 3138
40. TorarinssonELindgreenS 2008 WAR: Webserver for aligning structural RNAs. Nucleic Acids Res 36 W79 84
41. LindahlLZengelJM 1986 Ribosomal genes in Escherichia coli. Annu Rev Genet 20 297 326
42. VitreschakAGMironovAALyubetskyVAGelfandMS 2008 Comparative genomic analysis of T-box regulatory systems in bacteria. Rna 14 717 735
43. WarnerDFSavviSMizrahiVDawesSS 2007 A riboswitch regulates expression of the coenzyme B12-independent methionine synthase in Mycobacterium tuberculosis: implications for differential methionine synthase function in strains H37Rv and CDC1551. J Bacteriol 189 3655 3659
44. HobsonRJMcBrideAJKempsellKEDaleJW 2002 Use of an arrayed promoter-probe library for the identification of macrophage-regulated genes in Mycobacterium tuberculosis. Microbiology 148 1571 1579
45. RickmanLScottCHuntDMHutchinsonTMenendezMC 2005 A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol Microbiol 56 1274 1286
46. LunDSSherridAWeinerBShermanDRGalaganJE 2009 A blind deconvolution approach to high-resolution mapping of transcription factor binding sites from ChIP-seq data. Genome Biol 10 R142
47. RamanKChandraN 2008 Mycobacterium tuberculosis interactome analysis unravels potential pathways to drug resistance. BMC Microbiol 8 234
48. ManganelliRVoskuilMI Schoolnik GK, Smith I 2001 The Mycobacterium tuberculosis ECF sigma factor sigmaE: role in global gene expression and survival in macrophages. Mol Microbiol 41 423 437
49. SunRConversePJKoCTyagiSMorrisonNE 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
50. Munoz-EliasEJTimmJBothaTChanWTGomezJE 2005 Replication dynamics of Mycobacterium tuberculosis in chronically infected mice. Infect Immun 73 546 551
51. GillWPHarikNSWhiddonMRLiaoRPMittlerJE 2009 A replication clock for Mycobacterium tuberculosis. Nat Med 15 211 214
52. ReesRJHartPD 1961 Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br J Exp Pathol 42 83 88
53. ChaoMCRubinEJ 2010 Letting sleeping dos lie: does dormancy play a role in tuberculosis? Annu Rev Microbiol 64 293 311
54. KomorowskiMMiekiszJKierzekAM 2009 Translational repression contributes greater noise to gene expression than transcriptional repression. Biophys J 96 372 384
55. Vlietv 2010 Next generation sequencing of microbial transcriptomes: challenges and opportunities. FEMS Microiol Lett 302 1 7
56. JonesGJGordonSVHewinsonRGVordermeierHM 2010 Screening of predicted secreted antigens from Mycobacterium bovis reveals the immunodominance of the ESAT-6 protein family. Infect Immun 78 1326 1332
57. GeorgJHessWR 2011 cis-antisense RNA, another level of gene regulation in bacteria. Microbiol Mol Biol Rev 75 286 300
58. EpshteinVCardinaleCJRuckensteinAEBorukhovSNudlerE 2007 An allosteric path to transcription termination. Mol Cell 28 991 1001
59. UnniramanSPrakashRNagarajaV 2002 Conserved economics of transcription termination in eubacteria. Nucleic Acids Res 30 675 684
60. MitraAAngamuthuKNagarajaV 2008 Genome-wide analysis of the intrinsic terminators of transcription across the genus Mycobacterium. Tuberculosis 88 566 575
61. PulUWurmRArslanZGeissenRHofmannN 2010 Identification and characterization of E. coli CRISPR-cas promoters and their silencing by H-NS. Mol Microbiol 75 1495 1512
62. ChooneeNEvenSZigLPutzerH 2007 Ribosomal protein L20 controls expression of the Bacillus subtilis infC operon via a transcription attenuation mechanism. Nucleic Acids Res 35 1578 1588
63. HomuthGMogkASchumannW 1999 Post-transcriptional regulation of the Bacillus subtilis dnaK operon. Mol Microbiol 32 1183 1197
64. JagerSJagerAKlugG 2004 CIRCE is not involved in heat-dependent transcription of groESL but in stabilization of the mRNA 5’-end in Rhodobacter capsulatus. Nucleic Acids Res 32 386 396
65. DattaPShiLBibiNBalazsiGGennaroML 2011 Regulation of central metabolism genes of Mycobacterium tuberculosis by parallel feed-forward loops controlled by sigma factor E (σ(E)). J Bacteriol 193 1154 1160
66. MicklinghoffJCBreitingerKJSchmidtMGeffersREikmannsBJ 2009 Role of the transcriptional regulator RamB (Rv0465c) in the control of the glyoxylate cycle in Mycobacterium tuberculosis. J Bacteriol 191 7260 7269
67. BoshoffHIMyersTGCoppBRMcNeilMRWilsonMA 2004 The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem 279 40174 40184
68. TrotochaudAEWassarmanKM 2005 A highly conserved 6S RNA structure is required for regulation of transcription. Nat Struct Mol Biol 12 313 319
69. PanekJKrasnyLBobekJJezkovaEKorelusovaJ 2011 The suboptimal structures find the optimal RNAs: homology search for bacterial non-coding RNAs using suboptimal RNA structures. Nucleic Acids Res 39 3418 3426
70. KerenIMinamiSRubinELewisK 2011 Characterization and Transcriptome Analysis of Mycobacterium tuberculosis Persisters. MBio 2 e00100 00111
71. PapavinasasundaramKPAndersonCBrooksPCThomasNAMovahedzadehF 2001 Slow induction of RecA by DNA damage in Mycobacterium tuberculosis. Microbiology 147 3271 3279
72. SnapperSBMeltonREMustafaSKieserTJacobsWRJ 1990 Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol Microbiol 4 1911 1919
73. CroucherNJFookesMCPerkinsTTTurnerDJMargueratSB 2009 A simple method for directional transcriptome sequencing using Illumina technology. Nucleic Acids Res 37 e148
74. LiHHandsakerBWysokerAFennellTRuanJ 2009 The Sequence Alignment/Map format and SAMtools. Bioinformatics 25 2078 2079
75. HuntDMSaldanhaJWBrennanJFBenjaminPStromM 2008 Single nucleotide polymorphisms that cause structural changes in the cyclic AMP receptor protein transcriptional regulator of the tuberculosis vaccine strain Mycobacterium bovis BCG alter global gene expression without attenuating growth. Infect Immun 76 2227 2234
76. BenjaminiYHochbergY 1995 Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Series B Stat Methodol 57 289 300
77. SmootMEOnoKRuscheinskiJWangPLIdekerT 2011 Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27 431 432
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2011 Číslo 11
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Multiple Candidate Effectors from the Oomycete Pathogen Suppress Host Plant Immunity
- The Splicing Factor Proline-Glutamine Rich (SFPQ/PSF) Is Involved in Influenza Virus Transcription
- A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis
- SH3 Domain-Mediated Recruitment of Host Cell Amphiphysins by Alphavirus nsP3 Promotes Viral RNA Replication