#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Stress-Induced Small RNA Modulates Alpha-Rhizobial Cell Cycle Progression


Microorganisms frequently encounter adverse conditions unfavorable for cell proliferation. They have evolved diverse mechanisms, including transcriptional control and targeted protein degradation, to adjust cell cycle progression in response to environmental cues. Non-coding RNAs are widespread regulators of various cellular processes in all domains of life. In prokaryotes, trans-encoded small non-coding RNAs (trans-sRNAs) contribute to a rapid cellular response to changing environments, but so far have not been directly related to cell cycle regulation. Here, we report the first example of a trans-sRNA (EcpR1) with two experimentally confirmed targets in the core of cell cycle regulation and demonstrate that in the plant-symbiotic alpha-proteobacterium Sinorhizobium meliloti the regulatory mechanism involves base-pairing of this sRNA with the dnaA and gcrA mRNAs. Most trans-sRNAs are restricted to closely related species, but the stress-induced EcpR1 is broadly conserved in the order of Rhizobiales suggesting an evolutionary advantage conferred by ecpR1. It broadens the functional diversity of prokaryotic sRNAs and adds a new regulatory level to the mechanisms that contribute to interlinking stress responses with the cell cycle machinery.


Vyšlo v časopise: A Stress-Induced Small RNA Modulates Alpha-Rhizobial Cell Cycle Progression. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005153
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005153

Souhrn

Microorganisms frequently encounter adverse conditions unfavorable for cell proliferation. They have evolved diverse mechanisms, including transcriptional control and targeted protein degradation, to adjust cell cycle progression in response to environmental cues. Non-coding RNAs are widespread regulators of various cellular processes in all domains of life. In prokaryotes, trans-encoded small non-coding RNAs (trans-sRNAs) contribute to a rapid cellular response to changing environments, but so far have not been directly related to cell cycle regulation. Here, we report the first example of a trans-sRNA (EcpR1) with two experimentally confirmed targets in the core of cell cycle regulation and demonstrate that in the plant-symbiotic alpha-proteobacterium Sinorhizobium meliloti the regulatory mechanism involves base-pairing of this sRNA with the dnaA and gcrA mRNAs. Most trans-sRNAs are restricted to closely related species, but the stress-induced EcpR1 is broadly conserved in the order of Rhizobiales suggesting an evolutionary advantage conferred by ecpR1. It broadens the functional diversity of prokaryotic sRNAs and adds a new regulatory level to the mechanisms that contribute to interlinking stress responses with the cell cycle machinery.


Zdroje

1. Deng G, Sui G (2013) Noncoding RNA in oncogenesis: a new era of identifying key players. Int J Mol Sci 14: 18319–18349. doi: 10.3390/ijms140918319 24013378

2. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215–233. doi: 10.1016/j.cell.2009.01.002 19167326

3. He L, He X, Lim LP, de Stanchina E, Xuan Z, et al. (2007) A microRNA component of the p53 tumour suppressor network. Nature 447: 1130–1134. 17554337

4. Combier JP, Frugier F, de Billy F, Boualem A, El-Yahyaoui F, et al. (2006) MtHAP2-1 is a key transcriptional regulator of symbiotic nodule development regulated by microRNA169 in Medicago truncatula. Genes Dev 20: 3084–3088. 17114582

5. Bustos-Sanmamed P, Bazin J, Hartmann C, Crespi M, Lelandais-Brière C (2013) Small RNA pathways and diversity in model legumes: lessons from genomics. Front Plant Sci 4: 236. doi: 10.3389/fpls.2013.00236 23847640

6. Ding DQ, Okamasa K, Yamane M, Tsutsumi C, Haraguchi T, et al. (2012) Meiosis-specific noncoding RNA mediates robust pairing of homologous chromosomes in meiosis. Science 336: 732–736. doi: 10.1126/science.1219518 22582262

7. Yamashita A, Watanabe Y, Nukina N, Yamamoto M (1998) RNA-assisted nuclear transport of the meiotic regulator Mei2p in fission yeast. Cell 95: 115–123. 9778252

8. Waters LS, Storz G (2009) Regulatory RNAs in bacteria. Cell 136: 615–628. doi: 10.1016/j.cell.2009.01.043 19239884

9. Storz G, Vogel J, Wassarman KM (2011) Regulation by small RNAs in bacteria: expanding frontiers. Mol Cell 43: 880–891. doi: 10.1016/j.molcel.2011.08.022 21925377

10. Jonas K (2014) To divide or not to divide: control of the bacterial cell cycle by environmental cues. Curr Opin Microbiol 18: 54–60. doi: 10.1016/j.mib.2014.02.006 24631929

11. Tsokos CG, Laub MT (2012) Polarity and cell fate asymmetry in Caulobacter crescentus. Curr Opin Microbiol 15: 744–750. doi: 10.1016/j.mib.2012.10.011 23146566

12. Curtis PD, Brun YV (2010) Getting in the loop: regulation of development in Caulobacter crescentus. Microbiol Mol Biol Rev 74: 13–41. doi: 10.1128/MMBR.00040-09 20197497

13. Collier J, Murray SR, Shapiro L (2006) DnaA couples DNA replication and the expression of two cell cycle master regulators. EMBO J 25: 346–356. 16395331

14. McAdams HH, Shapiro L (2009) System-level design of bacterial cell cycle control. FEBS Lett 583: 3984–3991. doi: 10.1016/j.febslet.2009.09.030 19766635

15. Laub MT, Chen SL, Shapiro L, McAdams HH (2002) Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle. Proc Natl Acad Sci U S A 99: 4632–4637. 11930012

16. Marczynski GT, Shapiro L (2002) Control of chromosome replication in Caulobacter crescentus. Annu Rev Microbiol 56: 625–656. 12142494

17. Biondi EG, Reisinger SJ, Skerker JM, Arif M, Perchuk BS, et al. (2006) Regulation of the bacterial cell cycle by an integrated genetic circuit. Nature 444: 899–904. 17136100

18. Berghoff BA, Glaeser J, Sharma CM, Vogel J, Klug G (2009) Photooxidative stress-induced and abundant small RNAs in Rhodobacter sphaeroides. Mol Microbiol 74: 1497–1512. doi: 10.1111/j.1365-2958.2009.06949.x 19906181

19. Landt SG, Abeliuk E, McGrath PT, Lesley JA, McAdams HH, et al. (2008) Small non-coding RNAs in Caulobacter crescentus. Mol Microbiol 68: 600–614. doi: 10.1111/j.1365-2958.2008.06172.x 18373523

20. Becker A, Overlöper A, Schlüter JP, Reinkensmeier J, Robledo M, et al. (2014) Riboregulation in plant-associated α-proteobacteria. RNA Biol 11.

21. Schlüter JP, Reinkensmeier J, Daschkey S, Evguenieva-Hackenberg E, Janssen S, et al. (2010) A genome-wide survey of sRNAs in the symbiotic nitrogen-fixing alpha-proteobacterium Sinorhizobium meliloti. BMC Genomics 11: 245. doi: 10.1186/1471-2164-11-245 20398411

22. Schlüter JP, Reinkensmeier J, Barnett MJ, Lang C, Krol E, et al. (2013) Global mapping of transcription start sites and promoter motifs in the symbiotic α-proteobacterium Sinorhizobium meliloti 1021. BMC Genomics 14: 156. doi: 10.1186/1471-2164-14-156 23497287

23. Gibson KE, Kobayashi H, Walker GC (2008) Molecular determinants of a symbiotic chronic infection. Annu Rev Genet 42: 413–441. doi: 10.1146/annurev.genet.42.110807.091427 18983260

24. Jones KM, Kobayashi H, Davies BW, Taga ME, Walker GC (2007) How rhizobial symbionts invade plants: the Sinorhizobium-Medicago model. Nat Rev Microbiol 5: 619–633. 17632573

25. De Nisco NJ, Abo RP, Wu CM, Penterman J, Walker GC (2014) Global analysis of cell cycle gene expression of the legume symbiont Sinorhizobium meliloti. Proc Natl Acad Sci U S A.

26. Brilli M, Fondi M, Fani R, Mengoni A, Ferri L, et al. (2010) The diversity and evolution of cell cycle regulation in alpha-proteobacteria: a comparative genomic analysis. BMC Syst Biol 4: 52. doi: 10.1186/1752-0509-4-52 20426835

27. Reinkensmeier R, Schluter JP, Giegerich R, Becker A (2011) Conservation and occurrence of trans-encoded sRNAs in the Rhizobiales. Genes 2: 925–956 doi: 10.3390/genes2040925 24710299

28. Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, et al. (2013) Comparative genomics boosts target prediction for bacterial small RNAs. Proc Natl Acad Sci U S A 110: E3487–3496. doi: 10.1073/pnas.1303248110 23980183

29. Bouvier M, Sharma CM, Mika F, Nierhaus KH, Vogel J (2008) Small RNA binding to 5' mRNA coding region inhibits translational initiation. Mol Cell 32: 827–837. doi: 10.1016/j.molcel.2008.10.027 19111662

30. Sharma CM, Darfeuille F, Plantinga TH, Vogel J (2007) A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites. Genes Dev 21: 2804–2817. 17974919

31. del Val C, Rivas E, Torres-Quesada O, Toro N, Jiménez-Zurdo JI (2007) Identification of differentially expressed small non-coding RNAs in the legume endosymbiont Sinorhizobium meliloti by comparative genomics. Mol Microbiol 66: 1080–1091. 17971083

32. Pini F, Frage B, Ferri L, De Nisco NJ, Mohapatra SS, et al. (2013) The DivJ, CbrA and PleC system controls DivK phosphorylation and symbiosis in Sinorhizobium meliloti. Mol Microbiol 90: 54–71. doi: 10.1111/mmi.12347 23909720

33. Ulvé VM, Sevin EW, Chéron A, Barloy-Hubler F (2007) Identification of chromosomal alpha-proteobacterial small RNAs by comparative genome analysis and detection in Sinorhizobium meliloti strain 1021. BMC Genomics 8: 467. 18093320

34. Cheng J, Sibley CD, Zaheer R, Finan TM (2007) A Sinorhizobium meliloti minE mutant has an altered morphology and exhibits defects in legume symbiosis. Microbiology 153: 375–387. 17259609

35. Wright PR, Georg J, Mann M, Sorescu DA, Richter AS, et al. (2014) CopraRNA and IntaRNA: predicting small RNA targets, networks and interaction domains. Nucleic Acids Res 42: W119–123. doi: 10.1093/nar/gku359 24838564

36. Gruber AR, Lorenz R, Bernhart SH, Neuböck R, Hofacker IL (2008) The Vienna RNA websuite. Nucleic Acids Res 36: W70–74. doi: 10.1093/nar/gkn188 18424795

37. Valverde C, Livny J, Schlüter JP, Reinkensmeier J, Becker A, et al. (2008) Prediction of Sinorhizobium meliloti sRNA genes and experimental detection in strain 2011. BMC Genomics 9: 416. doi: 10.1186/1471-2164-9-416 18793445

38. Krol E, Becker A (2011) ppGpp in Sinorhizobium meliloti: biosynthesis in response to sudden nutritional downshifts and modulation of the transcriptome. Mol Microbiol 81: 1233–1254. doi: 10.1111/j.1365-2958.2011.07752.x 21696469

39. Sibley CD, MacLellan SR, Finan T (2006) The Sinorhizobium meliloti chromosomal origin of replication. Microbiology 152: 443–455. 16436432

40. Latch JN, Margolin W (1997) Generation of buds, swellings, and branches instead of filaments after blocking the cell cycle of Rhizobium meliloti. J Bacteriol 179: 2373–2381. 9079925

41. Kahng LS, Shapiro L (2001) The CcrM DNA methyltransferase of Agrobacterium tumefaciens is essential, and its activity is cell cycle regulated. J Bacteriol 183: 3065–3075. 11325934

42. Bahlawane C, McIntosh M, Krol E, Becker A (2008) Sinorhizobium meliloti regulator MucR couples exopolysaccharide synthesis and motility. Mol Plant Microbe Interact 21: 1498–1509. doi: 10.1094/MPMI-21-11-1498 18842098

43. Fields AT, Navarrete CS, Zare AZ, Huang Z, Mostafavi M, et al. (2012) The conserved polarity factor podJ1 impacts multiple cell envelope-associated functions in Sinorhizobium meliloti. Mol Microbiol 84: 892–920. doi: 10.1111/j.1365-2958.2012.08064.x 22553970

44. Torres-Quesada O, Millán V, Nisa-Martínez R, Bardou F, Crespi M, et al. (2013) Independent activity of the homologous small regulatory RNAs AbcR1 and AbcR2 in the legume symbiont Sinorhizobium meliloti. PLoS One 8: e68147. doi: 10.1371/journal.pone.0068147 23869210

45. Giacomini A, Ollero FJ, Squartini A, Nuti MP (1994) Construction of multipurpose gene cartridges based on a novel synthetic promoter for high-level gene expression in gram-negative bacteria. Gene 144: 17–24. 8026755

46. Greif D, Pobigaylo N, Frage B, Becker A, Regtmeier J, et al. (2010) Space- and time-resolved protein dynamics in single bacterial cells observed on a chip. J Biotechnol 149: 280–288. doi: 10.1016/j.jbiotec.2010.06.003 20599571

47. Galibert F, Finan TM, Long SR, Puhler A, Abola P, et al. (2001) The composite genome of the legume symbiont Sinorhizobium meliloti. Science 293: 668–672. 11474104

48. Gottesman S, Storz G (2011) Bacterial small RNA regulators: versatile roles and rapidly evolving variations. Cold Spring Harb Perspect Biol 3.

49. Rice JB, Vanderpool CK (2011) The small RNA SgrS controls sugar-phosphate accumulation by regulating multiple PTS genes. Nucleic Acids Res 39: 3806–3819. doi: 10.1093/nar/gkq1219 21245045

50. Desnoyers G, Morissette A, Prévost K, Massé E (2009) Small RNA-induced differential degradation of the polycistronic mRNA iscRSUA. EMBO J 28: 1551–1561. doi: 10.1038/emboj.2009.116 19407815

51. Majdalani N, Cunning C, Sledjeski D, Elliott T, Gottesman S (1998) DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription. Proc Natl Acad Sci U S A 95: 12462–12467. 9770508

52. Guillier M, Gottesman S (2008) The 5' end of two redundant sRNAs is involved in the regulation of multiple targets, including their own regulator. Nucleic Acids Res 36: 6781–6794. doi: 10.1093/nar/gkn742 18953042

53. Brennan RG, Link TM (2007) Hfq structure, function and ligand binding. Curr Opin Microbiol 10: 125–133. 17395525

54. Folichon M, Arluison V, Pellegrini O, Huntzinger E, Régnier P, et al. (2003) The poly(A) binding protein Hfq protects RNA from RNase E and exoribonucleolytic degradation. Nucleic Acids Res 31: 7302–7310. 14654705

55. Torres-Quesada O, Reinkensmeier J, Schlüter JP, Robledo M, Peregrina A, et al. (2014) Genome-wide profiling of Hfq-binding RNAs uncovers extensive post-transcriptional rewiring of major stress response and symbiotic regulons in Sinorhizobium meliloti. RNA Biol 11.

56. Torres-Quesada O, Oruezabal RI, Peregrina A, Jofré E, Lloret J, et al. (2010) The Sinorhizobium meliloti RNA chaperone Hfq influences central carbon metabolism and the symbiotic interaction with alfalfa. BMC Microbiol 10: 71. doi: 10.1186/1471-2180-10-71 20205931

57. Gao M, Barnett MJ, Long SR, Teplitski M (2010) Role of the Sinorhizobium meliloti global regulator Hfq in gene regulation and symbiosis. Mol Plant Microbe Interact 23: 355–365. doi: 10.1094/MPMI-23-4-0355 20192823

58. Morita T, Maki K, Aiba H (2005) RNase E-based ribonucleoprotein complexes: mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs. Genes Dev 19: 2176–2186. 16166379

59. Baumgardt K, Charoenpanich P, McIntosh M, Schikora A, Stein E, et al. (2014) RNase E affects the expression of the acyl-homoserine lactone synthase gene sinI in Sinorhizobium meliloti. J Bacteriol 196: 1435–1447. doi: 10.1128/JB.01471-13 24488310

60. Fioravanti A, Fumeaux C, Mohapatra SS, Bompard C, Brilli M, et al. (2013) DNA binding of the cell cycle transcriptional regulator GcrA depends on N6-adenosine methylation in Caulobacter crescentus and other Alphaproteobacteria. PLoS Genet 9: e1003541. doi: 10.1371/journal.pgen.1003541 23737758

61. Jonas K, Liu J, Chien P, Laub MT (2013) Proteotoxic stress induces a cell-cycle arrest by stimulating Lon to degrade the replication initiator DnaA. Cell 154: 623–636. doi: 10.1016/j.cell.2013.06.034 23911325

62. Tétart F, Bouché JP (1992) Regulation of the expression of the cell-cycle gene ftsZ by DicF antisense RNA. Division does not require a fixed number of FtsZ molecules. Mol Microbiol 6: 615–620. 1372677

63. Dadzie I, Xu S, Ni B, Zhang X, Zhang H, et al. (2013) Identification and characterization of a cis-encoded antisense RNA associated with the replication process of Salmonella enterica serovar Typhi. PLoS One 8: e61308. doi: 10.1371/journal.pone.0061308 23637809

64. Yu YT, Yuan X, Velicer GJ (2010) Adaptive evolution of an sRNA that controls Myxococcus development. Science 328: 993. doi: 10.1126/science.1187200 20489016

65. Grieshaber NA, Grieshaber SS, Fischer ER, Hackstadt T (2006) A small RNA inhibits translation of the histone-like protein Hc1 in Chlamydia trachomatis. Mol Microbiol 59: 541–550. 16390448

66. Tattersall J, Rao GV, Runac J, Hackstadt T, Grieshaber SS, et al. (2012) Translation inhibition of the developmental cycle protein HctA by the small RNA IhtA is conserved across Chlamydia. PLoS One 7: e47439. doi: 10.1371/journal.pone.0047439 23071807

67. Chant EL, Summers DK (2007) Indole signalling contributes to the stable maintenance of Escherichia coli multicopy plasmids. Mol Microbiol 63: 35–43. 17163976

68. Papenfort K, Pfeiffer V, Mika F, Lucchini S, Hinton JC, et al. (2006) SigmaE-dependent small RNAs of Salmonella respond to membrane stress by accelerating global omp mRNA decay. Mol Microbiol 62: 1674–1688. 17427289

69. Penterman J, Abo RP, De Nisco NJ, Arnold MF, Longhi R, et al. (2014) Host plant peptides elicit a transcriptional response to control the Sinorhizobium meliloti cell cycle during symbiosis. Proc Natl Acad Sci U S A.

70. Roux B, Rodde N, Jardinaud MF, Timmers T, Sauviac L, et al. (2014) An integrated analysis of plant and bacterial gene expression in symbiotic root nodules using laser-capture microdissection coupled to RNA sequencing. Plant J 77: 817–837. doi: 10.1111/tpj.12442 24483147

71. Braun RE, O'Day K, Wright A (1985) Autoregulation of the DNA replication gene dnaA in E. coli K-12. Cell 40: 159–169. 2981626

72. Holtzendorff J, Hung D, Brende P, Reisenauer A, Viollier PH, et al. (2004) Oscillating global regulators control the genetic circuit driving a bacterial cell cycle. Science 304: 983–987. 15087506

73. Zweiger G, Shapiro L (1994) Expression of Caulobacter dnaA as a function of the cell cycle. J Bacteriol 176: 401–408. 8288535

74. Desnoyers G, Bouchard MP, Massé E (2013) New insights into small RNA-dependent translational regulation in prokaryotes. Trends Genet 29: 92–98. doi: 10.1016/j.tig.2012.10.004 23141721

75. Corcoran CP, Podkaminski D, Papenfort K, Urban JH, Hinton JC, et al. (2012) Superfolder GFP reporters validate diverse new mRNA targets of the classic porin regulator, MicF RNA. Mol Microbiol 84: 428–445. doi: 10.1111/j.1365-2958.2012.08031.x 22458297

76. Rice JB, Balasubramanian D, Vanderpool CK (2012) Small RNA binding-site multiplicity involved in translational regulation of a polycistronic mRNA. Proc Natl Acad Sci U S A 109: E2691–2698. doi: 10.1073/pnas.1207927109 22988087

77. Beringer JE (1974) R factor transfer in Rhizobium leguminosarum. J Gen Microbiol 84: 188–198. 4612098

78. Zhan HJ, Lee CC, Leigh JA (1991) Induction of the second exopolysaccharide (EPSb) in Rhizobium meliloti SU47 by low phosphate concentrations. J Bacteriol 173: 7391–7394. 1938929

79. Robledo M, Jiménez-Zurdo JI, Velázquez E, Trujillo ME, Zurdo-Piñeiro JL, et al. (2008) Rhizobium cellulase CelC2 is essential for primary symbiotic infection of legume host roots. Proc Natl Acad Sci U S A 105: 7064–7069. doi: 10.1073/pnas.0802547105 18458328

80. Schäfer A, Tauch A, Jäger W, Kalinowski J, Thierbach G, et al. (1994) Small mobilizable multi-purpose cloning vectors derived from the Escherichia coli plasmids pK18 and pK19: selection of defined deletions in the chromosome of Corynebacterium glutamicum. Gene 145: 69–73. 8045426

81. McIntosh M, Meyer S, Becker A (2009) Novel Sinorhizobium meliloti quorum sensing positive and negative regulatory feedback mechanisms respond to phosphate availability. Mol Microbiol 74: 1238–1256. doi: 10.1111/j.1365-2958.2009.06930.x 19889097

82. Charoenpanich P, Meyer S, Becker A, McIntosh M (2013) Temporal expression program of quorum sensing-based transcription regulation in Sinorhizobium meliloti. J Bacteriol 195: 3224–3236. doi: 10.1128/JB.00234-13 23687265

83. Hübner P, Willison JC, Vignais PM, Bickle TA (1991) Expression of regulatory nif genes in Rhodobacter capsulatus. J Bacteriol 173: 2993–2999. 1902215

84. Serrania J, Vorhölter FJ, Niehaus K, Pühler A, Becker A (2008) Identification of Xanthomonas campestris pv. campestris galactose utilization genes from transcriptome data. J Biotechnol 135: 309–317. doi: 10.1016/j.jbiotec.2008.04.011 18538881

85. Dondrup M, Albaum SP, Griebel T, Henckel K, Jünemann S, et al. (2009) EMMA 2—a MAGE-compliant system for the collaborative analysis and integration of microarray data. BMC Bioinformatics 10: 50. doi: 10.1186/1471-2105-10-50 19200358

86. Becker A, Bergès H, Krol E, Bruand C, Rüberg S, et al. (2004) Global changes in gene expression in Sinorhizobium meliloti 1021 under microoxic and symbiotic conditions. Mol Plant Microbe Interact 17: 292–303. 15000396

87. Darty K, Denise A, Ponty Y (2009) VARNA: Interactive drawing and editing of the RNA secondary structure. Bioinformatics 25: 1974–1975. doi: 10.1093/bioinformatics/btp250 19398448

88. Smith C, Heyne S, Richter AS, Will S, Backofen R (2010) Freiburg RNA Tools: a web server integrating INTARNA, EXPARNA and LOCARNA. Nucleic Acids Res 38: W373–377. doi: 10.1093/nar/gkq316 20444875

89. R Core Team (2014). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. doi: 10.1016/j.jneumeth.2014.06.019 24970579

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#