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).

Secondary structure for the RyhB RNA. The Sm-like protein Hfq binds to the AU-rich unstructured region of RyhB as indicated. Below the secondary structure, the primary sequence of RyhB is shown along with its putative binding interaction to the target mRNA sodB. The start codon for sodB is underlined. RyhB nucleotides that participate in the interaction are in bold.[1]

Discovery

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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.[2][3]

Function and regulation

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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.[4] A number of other genes have been predicted computationally and verified as targets by microarray analysis: napF, sodA, cysE, yciS, acpS, nagZ and dadA.[1] 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

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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.[3] Other RNAs using this nomenclature include RydB RNA, RyeB RNA, RyeE RNA and RyfA RNA.

References

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  1. ^ a b Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX, Gottesman S, Storz G, et al. (2006). "Target prediction for small, noncoding RNAs in bacteria". Nucleic Acids Research. 34 (9): 2791–2802. doi:10.1093/nar/gkl356. PMC 1464411. PMID 16717284.
  2. ^ Argaman L, Hershberg R, Vogel J, Bejerano G, Wagner EG, Margalit H, Altuvia S (June 2001). "Novel small RNA-encoding genes in the intergenic regions of Escherichia coli". Current Biology. 11 (12): 941–950. doi:10.1016/S0960-9822(01)00270-6. PMID 11448770.
  3. ^ a b Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S (July 2001). "Identification of novel small RNAs using comparative genomics and microarrays". Genes & Development. 15 (13): 1637–1651. doi:10.1101/gad.901001. PMC 312727. PMID 11445539.
  4. ^ Massé E, Gottesman S (April 2002). "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. Bibcode:2002PNAS...99.4620M. doi:10.1073/pnas.032066599. PMC 123697. PMID 11917098.
  5. ^ Wright PR, Richter AS, Papenfort K, Mann M, Vogel J, Hess WR, Backofen R, Georg J (September 2013). "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. Bibcode:2013PNAS..110E3487W. doi:10.1073/pnas.1303248110. PMC 3773804. PMID 23980183.
  6. ^ Urban JH, Vogel J (2007). "Translational control and target recognition by Escherichia coli small RNAs in vivo". Nucleic Acids Research. 35 (3): 1018–1037. doi:10.1093/nar/gkl1040. PMC 1807950. PMID 17264113.
  7. ^ Desnoyers G, Morissette A, Prévost K, Massé E (June 2009). "Small RNA-induced differential degradation of the polycistronic mRNA iscRSUA". The EMBO Journal. 28 (11): 1551–1561. doi:10.1038/emboj.2009.116. PMC 2693151. PMID 19407815.
  8. ^ Neuhaus K, Landstorfer R, Simon S, Schober S, Wright PR, Smith C, Backofen R, Wecko R, Keim DA, Scherer S (February 2017). "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. doi:10.1186/s12864-017-3586-9. PMC 5331693. PMID 28245801.
  9. ^ Wilderman PJ, Sowa NA, FitzGerald DJ, FitzGerald PC, Gottesman S, Ochsner UA, Vasil ML (June 2004). "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. Bibcode:2004PNAS..101.9792W. doi:10.1073/pnas.0403423101. PMC 470753. PMID 15210934.
  10. ^ Santana EA, Harrison A, Zhang X, Baker BD, Kelly BJ, White P, Liu Y, Munson RS (2014-01-01). "HrrF is the Fur-regulated small RNA in nontypeable Haemophilus influenzae". PLOS ONE. 9 (8): e105644. Bibcode:2014PLoSO...9j5644S. doi:10.1371/journal.pone.0105644. PMC 4144887. PMID 25157846.
  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 (May 2017). "Acclimation of Oxygenic Photosynthesis to Iron Starvation Is Controlled by the sRNA IsaR1" (PDF). Current Biology. 27 (10): 1425–1436.e7. doi:10.1016/j.cub.2017.04.010. PMID 28479323.
  12. ^ Rübsam H, Kirsch F, Reimann V, Erban A, Kopka J, Hagemann M, Hess WR, Klähn S (February 2018). "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. doi:10.1111/1462-2920.14079. PMID 29468839. S2CID 4350134.
  13. ^ Zhang S, Liu S, Wu N, Yuan Y, Zhang W, Zhang Y (2018). "Escherichia coli by Reducing Cellular Metabolism". Frontiers in Microbiology. 9: 136. doi:10.3389/fmicb.2018.00136. PMC 5808207. PMID 29467745.

Further reading

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