RyhB explained

RyhB RNA is a 90 nucleotide RNA that down-regulates a set of iron-storage and iron-using proteins when iron is limiting; it is itself negatively regulated by the ferric uptake repressor protein, Fur (Ferric uptake regulator).

Discovery

The gene was independently identified in two screens, named RyhB by Wassarman et al. and called SrI by Argaman et al. and was found to be expressed only in stationary phase.^{[1] [2]}

Function and regulation

RyhB RNA levels are inversely correlated with mRNA levels for the sdhCDAB operon, encoding succinate dehydrogenase, as well as five other genes previously shown to be positively regulated by Fur by an unknown mechanism. These include two other genes encoding enzymes in the tricarboxylic acid cycle, acnA and fumA, two ferritin genes, ftnA and bfr, and a gene for superoxide dismutase, sodB.^[3] A number of other genes have been predicted computationally and verified as targets by microarray analysis: napF, sodA, cysE, yciS, acpS, nagZ and dadA.^[4] RyhB is bound by the Hfq protein, that increases its interaction with its target messages.

A comparative genomics target prediction approach suggests that the mRNAs of eleven additional iron containing proteins are controlled by RyhB in Escherichia coli. Two of those (erpA, nirB) and two additional targets that are not directly related to iron (nagZ, marA) were verified with a GFP reporter system.^{[5] [6]}

It has been shown that RyhB has a role in targeting the polycistronic transcript iscRSUA for differential degradation. RyhB binds to the second cistron of iscRSUA, which encodes machinery for biosynthesis of Fe-S clusters. This binding promotes cleavage of the downstream iscSUA transcript. This cleavage leaves the 5′ IscR transcript which is a transcriptional regulator responsible regulating several genes that depend on cellular Fe-S level.^[7]

More recent data indicate a potential dual function role for RyhB. In this capacity it may act both as an RNA-RNA interaction based regulator and as a transcript encoding for a small protein.^[8]

RyhB is analogous to PrrF RNA found in Pseudomonas aeruginosa,^[9] to HrrF RNA in Haemophilus species ^[10] and to IsaR1 in cyanobacteria.^{[11] [12]}

First sRNA shown to mediate persistence to antibiotics in E.coli. The finding may lead to discovery of novel treatments for persistent infections.^[13]

Naming

The RyhB gene name is an acronym composed of R for RNA, y for unknown function (after the protein naming convention), with the h representing the ten-minute-interval section of the E. coli map the gene is found in. The B comes from the fact that this was one of two RNA genes identified in this interval. Other RNAs using this nomenclature include RydB RNA, RyeB RNA, RyeE RNA and RyfA RNA.

Further reading

• Salvail H, Lanthier-Bourbonnais P, Sobota JM, Caza M, Benjamin JA, Mendieta ME, Lépine F, Dozois CM, Imlay J, Massé E . A small RNA promotes siderophore production through transcriptional and metabolic remodeling . Proceedings of the National Academy of Sciences of the United States of America . 107 . 34 . 15223–15228 . August 2010 . 20696910 . 2930555 . 10.1073/pnas.1007805107 . 2010PNAS..10715223S . free .
• Nandal A, Huggins CC, Woodhall MR, McHugh J, Rodríguez-Quiñones F, Quail MA, Guest JR, Andrews SC . Induction of the ferritin gene (ftnA) of Escherichia coli by Fe(2+)-Fur is mediated by reversal of H-NS silencing and is RyhB independent . Molecular Microbiology . 75 . 3 . 637–657 . February 2010 . 20015147 . 10.1111/j.1365-2958.2009.06977.x . 31281147 .
• Bollinger CJ, Kallio PT . Impact of the small RNA RyhB on growth, physiology and heterologous protein expression in Escherichia coli . FEMS Microbiology Letters . 275 . 2 . 221–228 . October 2007 . 17784860 . 10.1111/j.1574-6968.2007.00880.x . free . 20.500.11850/6259 . free .
• Prévost K, Salvail H, Desnoyers G, Jacques JF, Phaneuf E, Massé E . The small RNA RyhB activates the translation of shiA mRNA encoding a permease of shikimate, a compound involved in siderophore synthesis . Molecular Microbiology . 64 . 5 . 1260–1273 . June 2007 . 17542919 . 10.1111/j.1365-2958.2007.05733.x . free .
• Murphy ER, Payne SM . RyhB, an iron-responsive small RNA molecule, regulates Shigella dysenteriae virulence . Infection and Immunity . 75 . 7 . 3470–3477 . July 2007 . 17438026 . 1932958 . 10.1128/IAI.00112-07 .
• Vecerek B, Moll I, Bläsi U . Control of Fur synthesis by the non-coding RNA RyhB and iron-responsive decoding . The EMBO Journal . 26 . 4 . 965–975 . February 2007 . 17268550 . 1852835 . 10.1038/sj.emboj.7601553 .
• Jacques JF, Jang S, Prévost K, Desnoyers G, Desmarais M, Imlay J, Massé E . RyhB small RNA modulates the free intracellular iron pool and is essential for normal growth during iron limitation in Escherichia coli . Molecular Microbiology . 62 . 4 . 1181–1190 . November 2006 . 17078818 . 10.1111/j.1365-2958.2006.05439.x . free .
• Oglesby AG, Murphy ER, Iyer VR, Payne SM . Fur regulates acid resistance in Shigella flexneri via RyhB and ydeP . Molecular Microbiology . 58 . 5 . 1354–1367 . December 2005 . 16313621 . 10.1111/j.1365-2958.2005.04920.x . free .
• Massé E, Vanderpool CK, Gottesman S . Effect of RyhB small RNA on global iron use in Escherichia coli . Journal of Bacteriology . 187 . 20 . 6962–6971 . October 2005 . 16199566 . 1251601 . 10.1128/JB.187.20.6962-6971.2005 .
• Mey AR, Craig SA, Payne SM . Characterization of Vibrio cholerae RyhB: the RyhB regulon and role of ryhB in biofilm formation . Infection and Immunity . 73 . 9 . 5706–5719 . September 2005 . 16113288 . 1231101 . 10.1128/IAI.73.9.5706-5719.2005 .
• Davis BM, Quinones M, Pratt J, Ding Y, Waldor MK . Characterization of the small untranslated RNA RyhB and its regulon in Vibrio cholerae . Journal of Bacteriology . 187 . 12 . 4005–4014 . June 2005 . 15937163 . 1151736 . 10.1128/JB.187.12.4005-4014.2005 .
• Gottesman S . Micros for microbes: non-coding regulatory RNAs in bacteria . Trends in Genetics . 21 . 7 . 399–404 . July 2005 . 15913835 . 10.1016/j.tig.2005.05.008 . 10.1.1.391.8944 .
• Afonyushkin T, Vecerek B, Moll I, Bläsi U, Kaberdin VR . Both RNase E and RNase III control the stability of sodB mRNA upon translational inhibition by the small regulatory RNA RyhB . Nucleic Acids Research . 33 . 5 . 1678–1689 . 2005 . 15781494 . 1069011 . 10.1093/nar/gki313 .
• Oglesby-Sherrouse AG, Murphy ER . Iron-responsive bacterial small RNAs: variations on a theme . Metallomics . 5 . 4 . 276–286 . April 2013 . 23340911 . 3612141. 10.1039/c3mt20224k .
• Tanabe T, Funahashi T, Nakao H, Maki J, Yamamoto S . The Vibrio parahaemolyticus small RNA RyhB promotes production of the siderophore vibrioferrin by stabilizing the polycistronic mRNA . Journal of Bacteriology . 195 . 16 . 3692–3703 . August 2013 . 23772063 . 3754555 . 10.1128/JB.00162-13 .
• Bos J, Duverger Y, Thouvenot B, Chiaruttini C, Branlant C, Springer M, Charpentier B, Barras F . The sRNA RyhB regulates the synthesis of the Escherichia coli methionine sulfoxide reductase MsrB but not MsrA . PLOS ONE . 8 . 5 . e63647 . 2013 . 23671689 . 3650055 . 10.1371/journal.pone.0063647 . 2013PLoSO...863647B . Cascales . Eric . free .
• Deng Z, Liu Z, Bi Y, Wang X, Zhou D, Yang R, Han Y . Rapid degradation of Hfq-free RyhB in Yersinia pestis by PNPase independent of putative ribonucleolytic complexes . BioMed Research International . 2014 . 798918 . 2014 . 24818153 . 4003864 . 10.1155/2014/798918 . free .
• Li F, Wang Y, Gong K, Wang Q, Liang Q, Qi Q . Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli . FEMS Microbiology Letters . 350 . 2 . 209–215 . January 2014 . 24188714 . 10.1111/1574-6968.12322 . free .
• Porcheron G, Habib R, Houle S, Caza M, Lépine F, Daigle F, Massé E, Dozois CM . The small RNA RyhB contributes to siderophore production and virulence of uropathogenic Escherichia coli . Infection and Immunity . 82 . 12 . 5056–5068 . December 2014 . 25245805 . 4249264 . 10.1128/IAI.02287-14 .
• Calderón PF, Morales EH, Acuña LG, Fuentes DN, Gil F, Porwollik S, McClelland M, Saavedra CP, Calderón IL . The small RNA RyhB homologs from Salmonella typhimurium participate in the response to S-nitrosoglutathione-induced stress . Biochemical and Biophysical Research Communications . 450 . 1 . 641–645 . July 2014 . 24937451 . 10.1016/j.bbrc.2014.06.031 . free .

Notes and References

1. Argaman L, Hershberg R, Vogel J, Bejerano G, Wagner EG, Margalit H, Altuvia S . Novel small RNA-encoding genes in the intergenic regions of Escherichia coli . Current Biology . 11 . 12 . 941–950 . June 2001 . 11448770 . 10.1016/S0960-9822(01)00270-6 . free .
2. Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S . Identification of novel small RNAs using comparative genomics and microarrays . Genes & Development . 15 . 13 . 1637–1651 . July 2001 . 11445539 . 312727 . 10.1101/gad.901001 .
3. Massé E, Gottesman S . A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli . Proceedings of the National Academy of Sciences of the United States of America . 99 . 7 . 4620–4625 . April 2002 . 11917098 . 123697 . 10.1073/pnas.032066599 . 2002PNAS...99.4620M . free .
4. Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX, Gottesman S, Storz G . Target prediction for small, noncoding RNAs in bacteria . Nucleic Acids Research . 34 . 9 . 2791–2802 . 2006 . 16717284 . 1464411 . 10.1093/nar/gkl356 . etal .
5. Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R, Georg J . Comparative genomics boosts target prediction for bacterial small RNAs . Proceedings of the National Academy of Sciences of the United States of America . 110 . 37 . E3487–3496 . September 2013 . 23980183 . 3773804 . 10.1073/pnas.1303248110 . 2013PNAS..110E3487W . free .
6. Urban JH, Vogel J . Translational control and target recognition by Escherichia coli small RNAs in vivo . Nucleic Acids Research . 35 . 3 . 1018–1037 . 2007 . 17264113 . 1807950 . 10.1093/nar/gkl1040 .
7. Desnoyers G, Morissette A, Prévost K, Massé E . Small RNA-induced differential degradation of the polycistronic mRNA iscRSUA . The EMBO Journal . 28 . 11 . 1551–1561 . June 2009 . 19407815 . 2693151 . 10.1038/emboj.2009.116 .
8. Neuhaus K, Landstorfer R, Simon S, Schober S, Wright PR, Smith C, Backofen R, Wecko R, Keim DA, Scherer S . Differentiation of ncRNAs from small mRNAs in Escherichia coli O157:H7 EDL933 (EHEC) by combined RNAseq and RIBOseq - ryhB encodes the regulatory RNA RyhB and a peptide, RyhP . BMC Genomics . 18 . 1 . 216 . February 2017 . 28245801 . 5331693 . 10.1186/s12864-017-3586-9 . free .
9. Wilderman PJ, Sowa NA, FitzGerald DJ, FitzGerald PC, Gottesman S, Ochsner UA, Vasil ML . Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis . Proceedings of the National Academy of Sciences of the United States of America . 101 . 26 . 9792–9797 . June 2004 . 15210934 . 470753 . 10.1073/pnas.0403423101 . 2004PNAS..101.9792W . free .
10. Santana EA, Harrison A, Zhang X, Baker BD, Kelly BJ, White P, Liu Y, Munson RS . HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae . PLOS ONE . 9 . 8 . e105644 . 2014-01-01 . 25157846 . 4144887 . 10.1371/journal.pone.0105644 . 2014PLoSO...9j5644S . free .
11. Georg J, Kostova G, Vuorijoki L, Schön V, Kadowaki T, Huokko T, Baumgartner D, Müller M, Klähn S, Allahverdiyeva Y, Hihara Y, Futschik ME, Aro EM, Hess WR . Acclimation of Oxygenic Photosynthesis to Iron Starvation Is Controlled by the sRNA IsaR1 . Current Biology . 27 . 10 . 1425–1436.e7 . May 2017 . 28479323 . 10.1016/j.cub.2017.04.010 . free .
12. Rübsam H, Kirsch F, Reimann V, Erban A, Kopka J, Hagemann M, Hess WR, Klähn S . The iron-stress activated RNA 1 (IsaR1) coordinates osmotic acclimation and iron starvation responses in the cyanobacterium Synechocystis sp. PCC 6803 . Environmental Microbiology . 20 . 8 . 2757–2768 . February 2018 . 29468839 . 10.1111/1462-2920.14079 . 4350134 .
13. Zhang S, Liu S, Wu N, Yuan Y, Zhang W, Zhang Y . Escherichia coli by Reducing Cellular Metabolism . Frontiers in Microbiology . 9 . 136 . 2018 . 29467745 . 5808207 . 10.3389/fmicb.2018.00136 . free .