No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Small RNAs Involved in Regulation of Nitrogen Metabolism

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Daniela Prasse1, Ruth A. Schmitz2
  • Editors: Gisela Storz3, Kai Papenfort4
    Affiliations: 1: Christian-Albrechts-University Kiel, Institute of General Microbiology, D-24118 Kiel, Germany; 2: Christian-Albrechts-University Kiel, Institute of General Microbiology, D-24118 Kiel, Germany; 3: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 4: Department of Biology I, Microbiology, LMU Munich, Martinsried, Germany
  • Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0018-2018
  • Received 12 January 2018 Accepted 25 April 2018 Published 20 July 2018
  • Ruth A. Schmitz, [email protected]
image of Small RNAs Involved in Regulation of Nitrogen Metabolism
    Preview this microbiology spectrum article:
    Zoom in

    Small RNAs Involved in Regulation of Nitrogen Metabolism, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/6/4/RWR-0018-2018-1.gif /docserver/preview/fulltext/microbiolspec/6/4/RWR-0018-2018-2.gif
  • Abstract:

    Global (metabolic) regulatory networks allow microorganisms to survive periods of nitrogen starvation or general nutrient stress. Uptake and utilization of various nitrogen sources are thus commonly tightly regulated in ( and ) in response to available nitrogen sources. Those well-studied regulations occur mainly at the transcriptional and posttranslational level. Surprisingly, and in contrast to their involvement in most other stress responses, small RNAs (sRNAs) involved in the response to environmental nitrogen fluctuations are only rarely reported. In addition to sRNAs indirectly affecting nitrogen metabolism, only recently it was demonstrated that three sRNAs were directly involved in regulation of nitrogen metabolism in response to changes in available nitrogen sources. All three -acting sRNAs are under direct transcriptional control of global nitrogen regulators and affect expression of components of nitrogen metabolism (glutamine synthetase, nitrogenase, and PII-like proteins) by either masking the ribosome binding site and thus inhibiting translation initiation or stabilizing the respective target mRNAs. Most likely, there are many more sRNAs and other types of noncoding RNAs, e.g., riboswitches, involved in the regulation of nitrogen metabolism in that remain to be uncovered. The present review summarizes the current knowledge on sRNAs involved in nitrogen metabolism and their biological functions and targets.

  • Citation: Prasse D, Schmitz R. 2018. Small RNAs Involved in Regulation of Nitrogen Metabolism. Microbiol Spectrum 6(4):RWR-0018-2018. doi:10.1128/microbiolspec.RWR-0018-2018.


1. Fischer HM. 1994. Genetic regulation of nitrogen fixation in rhizobia. Microbiol Rev 58:352–386. [PubMed]
2. Kessler PS, McLarnan J, Leigh JA. 1997. Nitrogenase phylogeny and the molybdenum dependence of nitrogen fixation in Methanococcus maripaludis. J Bacteriol 179:541–543. http://dx.doi.org/10.1128/jb.179.2.541-543.1997. [PubMed]
3. Smith DR, Doucette-Stamm LA, Deloughery C, Lee H, Dubois J, Aldredge T, Bashirzadeh R, Blakely D, Cook R, Gilbert K, Harrison D, Hoang L, Keagle P, Lumm W, Pothier B, Qiu D, Spadafora R, Vicaire R, Wang Y, Wierzbowski J, Gibson R, Jiwani N, Caruso A, Bush D, Reeve JN. 1997. Complete genome sequence of Methanobacterium thermoautotrophicum ΔH: functional analysis and comparative genomics. J Bacteriol 179:7135–7155. http://dx.doi.org/10.1128/jb.179.22.7135-7155.1997. [PubMed]
4. Leigh JA. 2000. Nitrogen fixation in methanogens: the archaeal perspective. Curr Issues Mol Biol 2:125–131. [PubMed]
5. Dos Santos PC, Fang Z, Mason SW, Setubal JC, Dixon R. 2012. Distribution of nitrogen fixation and nitrogenase-like sequences amongst microbial genomes. BMC Genomics 13:162. http://dx.doi.org/10.1186/1471-2164-13-162. [PubMed]
6. Moure VR, Costa FF, Cruz LM, Pedrosa FO, Souza EM, Li XD, Winkler F, Huergo LF. 2015. Regulation of nitrogenase by reversible mono-ADP-ribosylation. Curr Top Microbiol Immunol 384:89–106. http://dx.doi.org/10.1007/82_2014_380. [PubMed]
7. Merrick M. 2015. Post-translational modification of P II signal transduction proteins. Front Microbiol 5:763. http://dx.doi.org/10.3389/fmicb.2014.00763. [PubMed]
8. Dixon R, Kahn D. 2004. Genetic regulation of biological nitrogen fixation. Nat Rev Microbiol 2:621–631. http://dx.doi.org/10.1038/nrmicro954.
9. Leigh JA, Dodsworth JA. 2007. Nitrogen regulation in Bacteria and Archaea. Annu Rev Microbiol 61:349–377. http://dx.doi.org/10.1146/annurev.micro.61.080706.093409. [PubMed]
10. Muro-Pastor MI, Reyes JC, Florencio FJ. 2005. Ammonium assimilation in cyanobacteria. Photosynth Res 83:135–150. http://dx.doi.org/10.1007/s11120-004-2082-7. [PubMed]
11. Herrero A, Muro-Pastor AM, Flores E. 2001. Nitrogen control in cyanobacteria. J Bacteriol 183:411–425. http://dx.doi.org/10.1128/JB.183.2.411-425.2001. [PubMed]
12. van Heeswijk WC, Westerhoff HV, Boogerd FC. 2013. Nitrogen assimilation in Escherichia coli: putting molecular data into a systems perspective. Microbiol Mol Biol Rev 77:628–695. http://dx.doi.org/10.1128/MMBR.00025-13. [PubMed]
13. Forchhammer K, Lüddecke J. 2016. Sensory properties of the PII signalling protein family. FEBS J 283:425–437. http://dx.doi.org/10.1111/febs.13584. [PubMed]
14. Schumacher J, Behrends V, Pan Z, Brown DR, Heydenreich F, Lewis MR, Bennett MH, Razzaghi B, Komorowski M, Barahona M, Stumpf MP, Wigneshweraraj S, Bundy JG, Buck M. 2013. Nitrogen and carbon status are integrated at the transcriptional level by the nitrogen regulator NtrC in vivo. mBio 4:e00881-e13. http://dx.doi.org/10.1128/mBio.00881-13. [PubMed]
15. Zehr JP. 2011. Nitrogen fixation by marine cyanobacteria. Trends Microbiol 19:162–173. http://dx.doi.org/10.1016/j.tim.2010.12.004. [PubMed]
16. Hoffman BM, Lukoyanov D, Yang ZY, Dean DR, Seefeldt LC. 2014. Mechanism of nitrogen fixation by nitrogenase: the next stage. Chem Rev 114:4041–4062. http://dx.doi.org/10.1021/cr400641x. [PubMed]
17. Seefeldt LC, Hoffman BM, Dean DR. 2009. Mechanism of Mo-dependent nitrogenase. Annu Rev Biochem 78:701–722. http://dx.doi.org/10.1146/annurev.biochem.78.070907.103812. [PubMed]
18. Huergo LF, Pedrosa FO, Muller-Santos M, Chubatsu LS, Monteiro RA, Merrick M, Souza EM. 2012. PII signal transduction proteins: pivotal players in post-translational control of nitrogenase activity. Microbiology 158:176–190. http://dx.doi.org/10.1099/mic.0.049783-0. [PubMed]
19. Masepohl B, Hallenbeck PC. 2010. Nitrogen and molybdenum control of nitrogen fixation in the phototrophic bacterium Rhodobacter capsulatus. Adv Exp Med Biol 675:49–70. http://dx.doi.org/10.1007/978-1-4419-1528-3_4. [PubMed]
20. Dodsworth JA, Leigh JA. 2006. Regulation of nitrogenase by 2-oxoglutarate-reversible, direct binding of a PII-like nitrogen sensor protein to dinitrogenase. Proc Natl Acad Sci U S A 103:9779–9784. http://dx.doi.org/10.1073/pnas.0602278103. [PubMed]
21. Leigh JA. 1999. Transcriptional regulation in Archaea. Curr Opin Microbiol 2:131–134. http://dx.doi.org/10.1016/S1369-5274(99)80023-X.
22. Cohen-Kupiec R, Blank C, Leigh JA. 1997. Transcriptional regulation in Archaea: in vivo demonstration of a repressor binding site in a methanogen. Proc Natl Acad Sci U S A 94:1316–1320. http://dx.doi.org/10.1073/pnas.94.4.1316. [PubMed]
23. Lie TJ, Leigh JA. 2003. A novel repressor of nif and glnA expression in the methanogenic archaeon Methanococcus maripaludis. Mol Microbiol 47:235–246. http://dx.doi.org/10.1046/j.1365-2958.2003.03293.x. [PubMed]
24. Weidenbach K, Glöer J, Ehlers C, Sandman K, Reeve JN, Schmitz RA. 2008. Deletion of the archaeal histone in Methanosarcina mazei Gö1 results in reduced growth and genomic transcription. Mol Microbiol 67:662–671. http://dx.doi.org/10.1111/j.1365-2958.2007.06076.x. [PubMed]
25. Lie TJ, Hendrickson EL, Niess UM, Moore BC, Haydock AK, Leigh JA. 2010. Overlapping repressor binding sites regulate expression of the Methanococcus maripaludisglnK 1 operon. Mol Microbiol 75:755–762. http://dx.doi.org/10.1111/j.1365-2958.2009.07016.x. [PubMed]
26. Weidenbach K, Ehlers C, Kock J, Schmitz RA. 2010. NrpRII mediates contacts between NrpRI and general transcription factors in the archaeon Methanosarcina mazei Gö1. FEBS J 277:4398–4411. http://dx.doi.org/10.1111/j.1742-4658.2010.07821.x. [PubMed]
27. Lie TJ, Wood GE, Leigh JA. 2005. Regulation of nif expression in Methanococcus maripaludis: roles of the euryarchaeal repressor NrpR, 2-oxoglutarate, and two operators. J Biol Chem 280:5236–5241. http://dx.doi.org/10.1074/jbc.M411778200. [PubMed]
28. Lie TJ, Leigh JA. 2007. Genetic screen for regulatory mutations in Methanococcus maripaludis and its use in identification of induction-deficient mutants of the euryarchaeal repressor NrpR. Appl Environ Microbiol 73:6595–6600. http://dx.doi.org/10.1128/AEM.01324-07. [PubMed]
29. Lie TJ, Dodsworth JA, Nickle DC, Leigh JA. 2007. Diverse homologues of the archaeal repressor NrpR function similarly in nitrogen regulation. FEMS Microbiol Lett 271:281–288. http://dx.doi.org/10.1111/j.1574-6968.2007.00726.x. [PubMed]
30. Weidenbach K, Ehlers C, Schmitz RA. 2014. The transcriptional activator NrpA is crucial for inducing nitrogen fixation in Methanosarcina mazei Gö1 under nitrogen-limited conditions. FEBS J 281:3507–3522. http://dx.doi.org/10.1111/febs.12876. [PubMed]
31. Wagner EG, 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. http://dx.doi.org/10.1016/bs.adgen.2015.05.001. [PubMed]
32. Mitschke J, Vioque A, Haas F, Hess WR, Muro-Pastor AM. 2011. Dynamics of transcriptional start site selection during nitrogen stress-induced cell differentiation in Anabaena sp. PCC7120. Proc Natl Acad Sci U S A 108:20130–20135. http://dx.doi.org/10.1073/pnas.1112724108. [PubMed]
33. Ionescu D, Voss B, Oren A, Hess WR, Muro-Pastor AM. 2010. Heterocyst-specific transcription of NsiR1, a non-coding RNA encoded in a tandem array of direct repeats in cyanobacteria. J Mol Biol 398:177–188. http://dx.doi.org/10.1016/j.jmb.2010.03.010. [PubMed]
34. Zhao J, Wolk CP. 2008. Developmental biology of heterocysts, 2006, p 397–418. In Whitworth DE (ed), Myxobacteria: Multicellularity and Differentiation. ASM Press, Washington, DC.
35. Muro-Pastor AM, Hess WR. 2012. Heterocyst differentiation: from single mutants to global approaches. Trends Microbiol 20:548–557. http://dx.doi.org/10.1016/j.tim.2012.07.005. [PubMed]
36. Muro-Pastor AM. 2014. The heterocyst-specific NsiR1 small RNA is an early marker of cell differentiation in cyanobacterial filaments. mBio 5:e01079-e14. http://dx.doi.org/10.1128/mBio.01079-14. [PubMed]
37. Olmedo-Verd E, Muro-Pastor AM, Flores E, Herrero A. 2006. Localized induction of the ntcA regulatory gene in developing heterocysts of Anabaena sp. strain PCC 7120. J Bacteriol 188:6694–6699. http://dx.doi.org/10.1128/JB.00509-06. [PubMed]
38. Rajagopalan R, Callahan SM. 2010. Temporal and spatial regulation of the four transcription start sites of hetR from Anabaena sp. strain PCC 7120. J Bacteriol 192:1088–1096. http://dx.doi.org/10.1128/JB.01297-09. [PubMed]
39. Barrick JE, Sudarsan N, Weinberg Z, Ruzzo WL, Breaker RR. 2005. 6S RNA is a widespread regulator of eubacterial RNA polymerase that resembles an open promoter. RNA 11:774–784. http://dx.doi.org/10.1261/rna.7286705. [PubMed]
40. Steuten B, Hoch PG, Damm K, Schneider S, Köhler K, Wagner R, Hartmann RK. 2014. Regulation of transcription by 6S RNAs: insights from the Escherichia coli and Bacillus subtilis model systems. RNA Biol 11:508–521. http://dx.doi.org/10.4161/rna.28827. [PubMed]
41. Cavanagh AT, Wassarman KM. 2014. 6S RNA, a global regulator of transcription in Escherichia coli, Bacillus subtilis, and beyond. Annu Rev Microbiol 68:45–60. http://dx.doi.org/10.1146/annurev-micro-092611-150135. [PubMed]
42. Burenina OY, Elkina DA, Hartmann RK, Oretskaya TS, Kubareva EA. 2015. Small noncoding 6S RNAs of bacteria. Biochemistry (Mosc) 80:1429–1446. http://dx.doi.org/10.1134/S0006297915110048. [PubMed]
43. Wassarman KM, Storz G. 2000. 6S RNA regulates E. coli RNA polymerase activity. Cell 101:613–623. http://dx.doi.org/10.1016/S0092-8674(00)80873-9.
44. Trotochaud AE, Wassarman KM. 2004. 6S RNA function enhances long-term cell survival. J Bacteriol 186:4978–4985. http://dx.doi.org/10.1128/JB.186.15.4978-4985.2004. [PubMed]
45. Cavanagh AT, Klocko AD, Liu X, Wassarman KM. 2008. Promoter specificity for 6S RNA regulation of transcription is determined by core promoter sequences and competition for region 4.2 of σ 70. Mol Microbiol 67:1242–1256. http://dx.doi.org/10.1111/j.1365-2958.2008.06117.x. [PubMed]
46. Neusser T, Polen T, Geissen R, Wagner R. 2010. Depletion of the non-coding regulatory 6S RNA in E. coli causes a surprising reduction in the expression of the translation machinery. BMC Genomics 11:165. http://dx.doi.org/10.1186/1471-2164-11-165. [PubMed]
47. Cavanagh AT, Sperger JM, Wassarman KM. 2012. Regulation of 6S RNA by pRNA synthesis is required for efficient recovery from stationary phase in E. coli and B. subtilis. Nucleic Acids Res 40:2234–2246. http://dx.doi.org/10.1093/nar/gkr1003. [PubMed]
48. Cabrera-Ostertag IJ, Cavanagh AT, Wassarman KM. 2013. Initiating nucleotide identity determines efficiency of RNA synthesis from 6S RNA templates in Bacillus subtilis but not Escherichia coli. Nucleic Acids Res 41:7501–7511. http://dx.doi.org/10.1093/nar/gkt517. [PubMed]
49. Heilmann B, Hakkila K, Georg J, Tyystjärvi T, Hess WR, Axmann IM, Dienst D. 2017. 6S RNA plays a role in recovery from nitrogen depletion in Synechocystis sp. PCC 6803. BMC Microbiol 17:229. http://dx.doi.org/10.1186/s12866-017-1137-9. [PubMed]
50. Klotz A, Georg J, Bučinská L, Watanabe S, Reimann V, Januszewski W, Sobotka R, Jendrossek D, Hess WR, Forchhammer K. 2016. Awakening of a dormant cyanobacterium from nitrogen chlorosis reveals a genetically determined program. Curr Biol 26:2862–2872. http://dx.doi.org/10.1016/j.cub.2016.08.054. [PubMed]
51. Asayama M, Imamura S, Yoshihara S, Miyazaki A, Yoshida N, Sazuka T, Kaneko T, Ohara O, Tabata S, Osanai T, Tanaka K, Takahashi H, Shirai M. 2004. SigC, the group 2 sigma factor of RNA polymerase, contributes to the late-stage gene expression and nitrogen promoter recognition in the cyanobacterium Synechocystis sp. strain PCC 6803. Biosci Biotechnol Biochem 68:477–487. http://dx.doi.org/10.1271/bbb.68.477. [PubMed]
52. Tuominen I, Tyystjärvi E, Tyystjärvi T. 2003. Expression of primary sigma factor (PSF) and PSF-like sigma factors in the cyanobacterium Synechocystis sp. strain PCC 6803. J Bacteriol 185:1116–1119. http://dx.doi.org/10.1128/JB.185.3.1116-1119.2003. [PubMed]
53. Livny J, Brencic A, Lory S, Waldor MK. 2006. Identification of 17 Pseudomonas aeruginosa sRNAs and prediction of sRNA-encoding genes in 10 diverse pathogens using the bioinformatic tool sRNAPredict2. Nucleic Acids Res 34:3484–3493. http://dx.doi.org/10.1093/nar/gkl453. [PubMed]
54. Romeo A, Sonnleitner E, Sorger-Domenigg T, Nakano M, Eisenhaber B, Bläsi U. 2012. Transcriptional regulation of nitrate assimilation in Pseudomonas aeruginosa occurs via transcriptional antitermination within the nirBD-PA1779-cobA operon. Microbiology 158:1543–1552. http://dx.doi.org/10.1099/mic.0.053850-0. [PubMed]
55. Moreno-Vivián C, Cabello P, Martínez-Luque M, Blasco R, Castillo F. 1999. Prokaryotic nitrate reduction: molecular properties and functional distinction among bacterial nitrate reductases. J Bacteriol 181:6573–6584. [PubMed]
56. Richardson DJ. 2001. Introduction: nitrate reduction and the nitrogen cycle. Cell Mol Life Sci 58:163–164. http://dx.doi.org/10.1007/PL00000844. [PubMed]
57. Lin JT, Stewart V. 1996. Nitrate and nitrite-mediated transcription antitermination control of nasF (nitrate assimilation) operon expression in Klebsiella pheumoniae M5al. J Mol Biol 256:423–435. http://dx.doi.org/10.1006/jmbi.1996.0098.
58. Setubal JC, dos Santos P, Goldman BS, Ertesvåg H, Espin G, Rubio LM, Valla S, Almeida NF, Balasubramanian D, Cromes L, Curatti L, Du Z, Godsy E, Goodner B, Hellner-Burris K, Hernandez JA, Houmiel K, Imperial J, Kennedy C, Larson TJ, Latreille P, Ligon LS, Lu J, Maerk M, Miller NM, Norton S, O’Carroll IP, Paulsen I, Raulfs EC, Roemer R, Rosser J, Segura D, Slater S, Stricklin SL, Studholme DJ, Sun J, Viana CJ, Wallin E, Wang B, Wheeler C, Zhu H, Dean DR, Dixon R, Wood D. 2009. Genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes. J Bacteriol 191:4534–4545. http://dx.doi.org/10.1128/JB.00504-09. [PubMed]
59. Rediers H, Vanderleyden J, De Mot R. 2004. Azotobacter vinelandii: a Pseudomonas in disguise? Microbiology 150:1117–1119. http://dx.doi.org/10.1099/mic.0.27096-0. [PubMed]
60. Chai W, Stewart V. 1998. NasR, a novel RNA-binding protein, mediates nitrate-responsive transcription antitermination of the Klebsiella oxytoca M5al nasF operon leader in vitro. J Mol Biol 283:339–351. http://dx.doi.org/10.1006/jmbi.1998.2105. [PubMed]
61. Gutierrez JC, Ramos F, Ortner L, Tortolero M. 1995. nasST, two genes involved in the induction of the assimilatory nitrite-nitrate reductase operon ( nasAB) of Azotobacter vinelandii. Mol Microbiol 18:579–591. http://dx.doi.org/10.1111/j.1365-2958.1995.mmi_18030579.x. [PubMed]
62. Stülke J. 2002. Control of transcription termination in bacteria by RNA-binding proteins that modulate RNA structures. Arch Microbiol 177:433–440. http://dx.doi.org/10.1007/s00203-002-0407-5. [PubMed]
63. Wenner N, Maes A, Cotado-Sampayo M, Lapouge K. 2014. NrsZ: a novel, processed, nitrogen-dependent, small non-coding RNA that regulates Pseudomonas aeruginosa PAO1 virulence. Environ Microbiol 16:1053–1068. http://dx.doi.org/10.1111/1462-2920.12272. [PubMed]
64. Maier RM, Soberón-Chávez G. 2000. Pseudomonas aeruginosa rhamnolipids: biosynthesis and potential applications. Appl Microbiol Biotechnol 54:625–633. http://dx.doi.org/10.1007/s002530000443. [PubMed]
65. Soberón-Chávez G, Lépine F, Déziel E. 2005. Production of rhamnolipids by Pseudomonas aeruginosa. Appl Microbiol Biotechnol 68:718–725. http://dx.doi.org/10.1007/s00253-005-0150-3. [PubMed]
66. Köhler T, Curty LK, Barja F, van Delden C, Pechère JC. 2000. Swarming of Pseudomonas aeruginosa is dependent on cell-to-cell signaling and requires flagella and pili. J Bacteriol 182:5990–5996. http://dx.doi.org/10.1128/JB.182.21.5990-5996.2000. [PubMed]
67. Déziel E, Lépine F, Milot S, Villemur R. 2003. rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs), the precursors of rhamnolipids. Microbiology 149:2005–2013. http://dx.doi.org/10.1099/mic.0.26154-0. [PubMed]
68. De Lay N, Gottesman S. 2009. The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior. J Bacteriol 191:461–476. http://dx.doi.org/10.1128/JB.01157-08. [PubMed]
69. Saier MH Jr. 1998. Multiple mechanisms controlling carbon metabolism in bacteria. Biotechnol Bioeng 58:170–174. http://dx.doi.org/10.1002/(SICI)1097-0290(19980420)58:2/3<170::AID-BIT9>3.0.CO;2-I.
70. Görke B, Stülke J. 2008. Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613–624. http://dx.doi.org/10.1038/nrmicro1932. [PubMed]
71. Deutscher J. 2008. The mechanisms of carbon catabolite repression in bacteria. Curr Opin Microbiol 11:87–93. http://dx.doi.org/10.1016/j.mib.2008.02.007. [PubMed]
72. 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. http://dx.doi.org/10.1101/gad.447207. [PubMed]
73. Sharma CM, Papenfort K, Pernitzsch SR, Mollenkopf HJ, Hinton JC, Vogel J. 2011. Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA. Mol Microbiol 81:1144–1165. http://dx.doi.org/10.1111/j.1365-2958.2011.07751.x. [PubMed]
74. Hao Y, Updegrove TB, Livingston NN, Storz G. 2016. Protection against deleterious nitrogen compounds: role of σ S-dependent small RNAs encoded adjacent to sdiA. Nucleic Acids Res 44:6935–6948. http://dx.doi.org/10.1093/nar/gkw404. [PubMed]
75. Zafar MA, Carabetta VJ, Mandel MJ, Silhavy TJ. 2014. Transcriptional occlusion caused by overlapping promoters. Proc Natl Acad Sci U S A 111:1557–1561. http://dx.doi.org/10.1073/pnas.1323413111. [PubMed]
76. Stewart V. 1994. Dual interacting two-component regulatory systems mediate nitrate- and nitrite-regulated gene expression in Escherichia coli. Res Microbiol 145:450–454. http://dx.doi.org/10.1016/0923-2508(94)90093-0.
77. Durand S, Braun F, Lioliou E, Romilly C, Helfer AC, Kuhn L, Quittot N, Nicolas P, Romby P, Condon C. 2015. A nitric oxide regulated small RNA controls expression of genes involved in redox homeostasis in Bacillus subtilis. PLoS Genet 11:e1004957. http://dx.doi.org/10.1371/journal.pgen.1004957. [PubMed]
78. Bandyra KJ, Said N, Pfeiffer V, Górna MW, Vogel J, Luisi BF. 2012. The seed region of a small RNA drives the controlled destruction of the target mRNA by the endoribonuclease RNase E. Mol Cell 47:943–953. http://dx.doi.org/10.1016/j.molcel.2012.07.015. [PubMed]
79. Papenfort K, Espinosa E, Casadesús J, Vogel J. 2015. Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella. Proc Natl Acad Sci U S A 112:E4772–E4781. http://dx.doi.org/10.1073/pnas.1507825112. [PubMed]
80. Jung YS, Kwon YM. 2008. Small RNA ArrF regulates the expression of sodB and feSII genes in Azotobacter vinelandii. Curr Microbiol 57:593–597. http://dx.doi.org/10.1007/s00284-008-9248-z. [PubMed]
81. Moshiri F, Kim JW, Fu C, Maier RJ. 1994. The FeSII protein of Azotobacter vinelandii is not essential for aerobic nitrogen fixation, but confers significant protection to oxygen-mediated inactivation of nitrogenase in vitro and in vivo. Mol Microbiol 14:101–114. http://dx.doi.org/10.1111/j.1365-2958.1994.tb01270.x. [PubMed]
82. Muriel-Millán LF, Castellanos M, Hernandez-Eligio JA, Moreno S, Espín G. 2014. Posttranscriptional regulation of PhbR, the transcriptional activator of polyhydroxybutyrate synthesis, by iron and the sRNA ArrF in Azotobacter vinelandii. Appl Microbiol Biotechnol 98:2173–2182. http://dx.doi.org/10.1007/s00253-013-5407-7. [PubMed]
83. Ceizel Borella G, Lagares A Jr, Valverde C. 2016. Expression of the Sinorhizobium meliloti small RNA gene mmgR is controlled by the nitrogen source. FEMS Microbiol Lett 363:fnw069. http://dx.doi.org/10.1093/femsle/fnw069. [PubMed]
84. Lagares A Jr, Ceizel Borella G, Linne U, Becker A, Valverde C. 2017. Regulation of polyhydroxybutyrate accumulation in Sinorhizobium meliloti by the trans-encoded small RNA MmgR. J Bacteriol 199:e00776-16. http://dx.doi.org/10.1128/JB.00776-16. [PubMed]
85. Ow DW, Sundaresan V, Rothstein DM, Brown SE, Ausubel FM. 1983. Promoters regulated by the glnG ( ntrC) and nifA gene products share a heptameric consensus sequence in the −15 region. Proc Natl Acad Sci U S A 80:2524–2528. http://dx.doi.org/10.1073/pnas.80.9.2524.
86. Ceizel Borella G, Lagares A Jr, Valverde C. 2018. Expression of the small regulatory RNA gene mmgR is regulated negatively by AniA and positively by NtrC in Sinorhizobium meliloti 2011. Microbiology 164:88–98. http://dx.doi.org/10.1099/mic.0.000586. [PubMed]
87. Jäger D, Sharma CM, Thomsen J, Ehlers C, Vogel J, Schmitz RA. 2009. Deep sequencing analysis of the Methanosarcina mazei Gö1 transcriptome in response to nitrogen availability. Proc Natl Acad Sci U S A 106:21878–21882. http://dx.doi.org/10.1073/pnas.0909051106. [PubMed]
88. Buddeweg A, Sharma K, Urlaub H, Schmitz RA. 2018. sRNA 41 affects ribosome binding sites within polycistronic mRNAs in Methanosarcina mazei Gö1. Mol Microbiol 107:595–609. http://dx.doi.org/10.1111/mmi.13900. [PubMed]
89. Kopf M, Klähn S, Scholz I, Hess WR, Voß B. 2015. Variations in the non-coding transcriptome as a driver of inter-strain divergence and physiological adaptation in bacteria. Sci Rep 5:9560. http://dx.doi.org/10.1038/srep09560. [PubMed]
90. Kopf M, Klähn S, Pade N, Weingärtner C, Hagemann M, Voß B, Hess WR. 2014. Comparative genome analysis of the closely related Synechocystis strains PCC 6714 and PCC 6803. DNA Res 21:255–266. http://dx.doi.org/10.1093/dnares/dst055. [PubMed]
91. Giner-Lamia J, Robles-Rengel R, Hernández-Prieto MA, Muro-Pastor MI, Florencio FJ, Futschik ME. 2017. Identification of the direct regulon of NtcA during early acclimation to nitrogen starvation in the cyanobacterium Synechocystis sp. PCC 6803. Nucleic Acids Res 45:11800–11820. http://dx.doi.org/10.1093/nar/gkx860. [PubMed]
92. Klähn S, Schaal C, Georg J, Baumgartner D, Knippen G, Hagemann M, Muro-Pastor AM, Hess WR. 2015. The sRNA NsiR4 is involved in nitrogen assimilation control in cyanobacteria by targeting glutamine synthetase inactivating factor IF7. Proc Natl Acad Sci U S A 112:E6243–E6252. http://dx.doi.org/10.1073/pnas.1508412112. [PubMed]
93. Golden JW, Yoon HS. 2003. Heterocyst development in Anabaena. Curr Opin Microbiol 6:557–563. http://dx.doi.org/10.1016/j.mib.2003.10.004.
94. Wright PR, Georg J, Mann M, Sorescu DA, Richter AS, Lott S, Kleinkauf R, Hess WR, Backofen R. 2014. CopraRNA and IntaRNA: predicting small RNA targets, networks and interaction domains. Nucleic Acids Res 42(Web Server issue) :W119–W123. http://dx.doi.org/10.1093/nar/gku359.
95. Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R, Georg J. 2013. Comparative genomics boosts target prediction for bacterial small RNAs. Proc Natl Acad Sci U S A 110:E3487–E3496. http://dx.doi.org/10.1073/pnas.1303248110. [PubMed]
96. Urban JH, Vogel J. 2009. A green fluorescent protein (GFP)-based plasmid system to study post-transcriptional control of gene expression in vivo. Methods Mol Biol 540:301–319. http://dx.doi.org/10.1007/978-1-59745-558-9_22. [PubMed]
97. Urban JH, Vogel J. 2007. Translational control and target recognition by Escherichia coli small RNAs in vivo. Nucleic Acids Res 35:1018–1037. http://dx.doi.org/10.1093/nar/gkl1040. [PubMed]
98. Ames TD, Breaker RR. 2011. Bacterial aptamers that selectively bind glutamine. RNA Biol 8:82–89. http://dx.doi.org/10.4161/rna.8.1.13864.
99. Ren A, Xue Y, Peselis A, Serganov A, Al-Hashimi HM, Patel DJ. 2015. Structural and dynamic basis for low-affinity, high-selectivity binding of l-glutamine by the glutamine riboswitch. Cell Rep 13:1800–1813. http://dx.doi.org/10.1016/j.celrep.2015.10.062. [PubMed]
100. Yan Y, Yang J, Dou Y, Chen M, Ping S, Peng J, Lu W, Zhang W, Yao Z, Li H, Liu W, He S, Geng L, Zhang X, Yang F, Yu H, Zhan Y, Li D, Lin Z, Wang Y, Elmerich C, Lin M, Jin Q. 2008. Nitrogen fixation island and rhizosphere competence traits in the genome of root-associated Pseudomonas stutzeri A1501. Proc Natl Acad Sci U S A 105:7564–7569. http://dx.doi.org/10.1073/pnas.0801093105. [PubMed]
101. Yu H, Yuan M, Lu W, Yang J, Dai S, Li Q, Yang Z, Dong J, Sun L, Deng Z, Zhang W, Chen M, Ping S, Han Y, Zhan Y, Yan Y, Jin Q, Lin M. 2011. Complete genome sequence of the nitrogen-fixing and rhizosphere-associated bacterium Pseudomonas stutzeri strain DSM4166. J Bacteriol 193:3422–3423. http://dx.doi.org/10.1128/JB.05039-11. [PubMed]
102. Bentzon-Tilia M, Severin I, Hansen LH, Riemann L. 2015. Genomics and ecophysiology of heterotrophic nitrogen-fixing bacteria isolated from estuarine surface water. mBio 6:e00929. http://dx.doi.org/10.1128/mBio.00929-15. [PubMed]
103. Yan Y, Lu W, Chen M, Wang J, Zhang W, Zhang Y, Ping S, Elmerich C, Lin M.2013. Genome transcriptome analysis and functional characterization of a nitrogen-fixation island in root-associated Pseudomonas stutzeri, p 851–863. In de Bruijn FJ (ed), Molecular Microbial Ecology of the Rhizosphere. John Wiley & Sons, Inc, New York, NY. doi:10.1002/9781118297674.ch80.
104. Zhan Y, Yan Y, Deng Z, Chen M, Lu W, Lu C, Shang L, Yang Z, Zhang W, Wang W, Li Y, Ke Q, Lu J, Xu Y, Zhang L, Xie Z, Cheng Q, Elmerich C, Lin M. 2016. The novel regulatory ncRNA, NfiS, optimizes nitrogen fixation via base pairing with the nitrogenase gene nifK mRNA in Pseudomonas stutzeri A1501. Proc Natl Acad Sci U S A 113:E4348–E4356. http://dx.doi.org/10.1073/pnas.1604514113. [PubMed]
105. Busch A, Richter AS, Backofen R. 2008. IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions. Bioinformatics 24:2849–2856. http://dx.doi.org/10.1093/bioinformatics/btn544. [PubMed]
106. Prasse D, Förstner KU, Jäger D, Backofen R, Schmitz RA. 2017. sRNA 154 a newly identified regulator of nitrogen fixation in Methanosarcina mazei strain Gö1. RNA Biol 14:1544–1558. http://dx.doi.org/10.1080/15476286.2017.1306170. [PubMed]
107. Sharma CM, Vogel J. 2014. Differential RNA-seq: the approach behind and the biological insight gained. Curr Opin Microbiol 19:97–105. http://dx.doi.org/10.1016/j.mib.2014.06.010. [PubMed]
108. Hervás AB, Canosa I, Little R, Dixon R, Santero E. 2009. NtrC-dependent regulatory network for nitrogen assimilation in Pseudomonas putida. J Bacteriol 191:6123–6135. http://dx.doi.org/10.1128/JB.00744-09. [PubMed]
109. Baumgartner D, Kopf M, Klähn S, Steglich C, Hess WR. 2016. Small proteins in cyanobacteria provide a paradigm for the functional analysis of the bacterial micro-proteome. BMC Microbiol 16:285. http://dx.doi.org/10.1186/s12866-016-0896-z. [PubMed]
110. Miseta A, Csutora P. 2000. Relationship between the occurrence of cysteine in proteins and the complexity of organisms. Mol Biol Evol 17:1232–1239. http://dx.doi.org/10.1093/oxfordjournals.molbev.a026406. [PubMed]
111. Prasse D, Thomsen J, De Santis R, Muntel J, Becher D, Schmitz RA. 2015. First description of small proteins encoded by spRNAs in Methanosarcina mazei strain Gö1. Biochimie 117:138–148. http://dx.doi.org/10.1016/j.biochi.2015.04.007. [PubMed]
112. Cassidy L, Prasse D, Linke D, Schmitz RA, Tholey A. 2016. Combination of bottom-up 2D-LC-MS and semi-top-down GelFree-LC-MS enhances coverage of proteome and low molecular weight short open reading frame encoded peptides of the archaeon Methanosarcina mazei. J Proteome Res 15:3773–3783. http://dx.doi.org/10.1021/acs.jproteome.6b00569. [PubMed]

Article metrics loading...



Global (metabolic) regulatory networks allow microorganisms to survive periods of nitrogen starvation or general nutrient stress. Uptake and utilization of various nitrogen sources are thus commonly tightly regulated in ( and ) in response to available nitrogen sources. Those well-studied regulations occur mainly at the transcriptional and posttranslational level. Surprisingly, and in contrast to their involvement in most other stress responses, small RNAs (sRNAs) involved in the response to environmental nitrogen fluctuations are only rarely reported. In addition to sRNAs indirectly affecting nitrogen metabolism, only recently it was demonstrated that three sRNAs were directly involved in regulation of nitrogen metabolism in response to changes in available nitrogen sources. All three -acting sRNAs are under direct transcriptional control of global nitrogen regulators and affect expression of components of nitrogen metabolism (glutamine synthetase, nitrogenase, and PII-like proteins) by either masking the ribosome binding site and thus inhibiting translation initiation or stabilizing the respective target mRNAs. Most likely, there are many more sRNAs and other types of noncoding RNAs, e.g., riboswitches, involved in the regulation of nitrogen metabolism in that remain to be uncovered. The present review summarizes the current knowledge on sRNAs involved in nitrogen metabolism and their biological functions and targets.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Nitrogen metabolism and regulation. The main components of nitrogen metabolism are depicted in a simplified way. Under nitrogen limitation (left), the GS with high binding affinity to ammonium (NH ) is activated. The remaining NH is actively transferred by ammonia transporters (AmtB) into the cell and dinitrogen (N) directly reduced into ammonium by the key enzyme nitrogenase. Subsequently, NH is assimilated by the GS and the GOGAT system. Under nitrogen sufficiency (right), the GS is inhibited and ammonia diffuses over the cytoplasm membrane into the cell, which can be directly assimilated by the glutamate dehydrogenase (low affinity). PII-like proteins are involved in most regulatory ways, sensing the current nitrogen status within the cell and forwarding the respective signal to GS, inducing reversible deactivation of GS by covalent modifications or direct interactions with proteins in response to the nitrogen availability, but also to nitrogenase and ammonia transporters (for details, see reference 9 ).

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0018-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Visualization of microorganisms for which currently known sRNAs are directly or indirectly involved in nitrogen metabolism and their phylogenetic distribution. Organisms belonging to the two different phylogenetic domains of and are colored and single organisms are exemplarily indicated. Each organism is depicted with its attendant sRNAs. sp. image obtained with confocal microscopy; , light microscopy; , fluorescence phase-contrast microscopy; and and , scanning electron microscopy.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0018-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Functional mechanisms of three sRNAs directly involved in regulation of nitrogen fixation. (A) The sRNA is a central regulatory component within the regulatory network of nitrogen fixation in strain Gö1. It was shown that sRNA acts on several target mRNAs by either stabilizing the mRNA by direct binding (in case of , , and operon) or repressing translation initiation by blocking the RBS (in case of ). In addition, sRNA-mediated regulation allows feedforward regulation of expression via mRNA stabilization. (B) In A1501, sRNA NfiS targets mRNA (possibly multiple times) and enhances transcript stability, very similar to sRNA in , which also targets and operon, possibly at multiple regions. (C) NsiR4 from 6803 interacts with mRNA, which encodes GS-inactivation factor 7, and blocks translation initiation by targeting the 5′ UTR of , consequently leading to a positive effect on GS activity under nitrogen limitation. This mode of action is very similar to that of sRNA, which targets the 5′ UTR of the transcript as well and represses translation initiation. post-tcript, posttranscriptional.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0018-2018
Permissions and Reprints Request Permissions
Download as Powerpoint


Generic image for table

sRNAs involved in nitrogen metabolism and their specific characteristics

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0018-2018

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error