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Small RNA regulators in bacteria: powerful tools for metabolic engineering and synthetic biology

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Abstract

Small RNAs, a large class of ancient posttranscriptional regulators, have recently attracted considerable attention. A plethora of small RNAs has been identified and characterized, many of which belong to the major small noncoding RNA (sRNA) or riboswitch families. It has become increasingly clear that most small RNAs play critical regulatory roles in many processes and are, therefore, considered to be powerful tools for metabolic engineering and synthetic biology. In this review, we describe recent achievements in the identification, characterization, and application of small RNAs. We give particular attention to advances in the design and synthesis of novel sRNAs and riboswitches for metabolic engineering. In addition, a novel strategy for hierarchical control of global metabolic pathways is proposed.

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References

  • Alon U (2007) Network motifs: theory and experimental approaches. Nat Rev Genet 8:450–461

    PubMed  CAS  Google Scholar 

  • Alper H, Moxley J, Nevoigt E, Fink GR, Stephanopoulos G (2006) Engineering yeast transcription machinery for improved ethanol tolerance and production. Science 314:1565–1568

    PubMed  CAS  Google Scholar 

  • Alper H, Stephanopoulos G (2007) Global transcription machinery engineering: a new approach for improving cellular phenotype. Metab Eng 9:258–267

    PubMed  CAS  Google Scholar 

  • Altuvia S (2007) Identification of bacterial small non-coding RNAs: experimental approaches. Curr Opin Microbiol 10:257–261

    PubMed  CAS  Google Scholar 

  • Altuvia S, Wagner EG (2000) Switching on and off with RNA. Proc Natl Acad Sci U S A 97:9824–9826

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ames TD, Breaker RR (2011) Bacterial aptamers that selectively bind glutamine. RNA Biol 8:82–89

    PubMed Central  PubMed  CAS  Google Scholar 

  • Balasubramanian D, Vanderpool CK (2013) Deciphering the interplay between two independent functions of the small RNA regulator SgrS in Salmonella. J Bacteriol 195:4620–4630

    PubMed Central  PubMed  CAS  Google Scholar 

  • Barrick JE, Breaker RR (2007) The distributions, mechanisms, and structures of metabolite-binding riboswitches. Genome Biol 8:R239

    PubMed Central  PubMed  Google Scholar 

  • Barrick JE, Corbino KA, Winkler WC, Nahvi A, Mandal M, Collins J, Lee M, Roth A, Sudarsan N, Jona I, Wickiser JK, Breaker RR (2004) New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proc Natl Acad Sci U S A 101:6421–6426

    PubMed Central  PubMed  CAS  Google Scholar 

  • Bayer TS, Smolke CD (2005) Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat Biotechnol 23:337–343

    PubMed  CAS  Google Scholar 

  • Beisel CL, Storz G (2010) Base pairing small RNAs and their roles in global regulatory networks. FEMS Microbiol Rev 34:866–882

    PubMed Central  PubMed  CAS  Google Scholar 

  • Benenson Y (2012) Synthetic biology with RNA: progress report. Curr Opin Chem Biol 16:278–284

    PubMed  CAS  Google Scholar 

  • Blouin S, Mulhbacher J, Penedo JC, Lafontaine DA (2009) Riboswitches: ancient and promising genetic regulators. Chembiochem 10:400–416

    PubMed  CAS  Google Scholar 

  • Boehm A, Vogel J (2012) The csgD mRNA as a hub for signal integration via multiple small RNAs. Mol Microbiol 84:1–5

    PubMed  CAS  Google Scholar 

  • Breaker RR (2008) Complex riboswitches. Science 319:1795–1797

    PubMed  CAS  Google Scholar 

  • Breaker RR (2012) Riboswitches and the RNA world. CSH Perspect Biol 4

  • Ceres P, Garst AD, Marcano-Velazquez JG, Batey RT (2013) Modularity of select riboswitch expression platforms enables facile engineering of novel genetic regulatory devices. ACS Synth Biol 2:463–472

    PubMed  CAS  Google Scholar 

  • Chappell J, Takahashi MK, Meyer S, Loughrey D, Watters KE, Lucks J (2013) The centrality of RNA for engineering gene expression. Biotechnol J 8:1379–1395

    PubMed  CAS  Google Scholar 

  • Chen Y, Nielsen J (2013) Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks. Curr Opin Biotechnol 24:965–972

    PubMed  CAS  Google Scholar 

  • Chen Z, Wilmanns M, Zeng AP (2010) Structural synthetic biotechnology: from molecular structure to predictable design for industrial strain development. Trends Biotechnol 28:534–542

    PubMed  CAS  Google Scholar 

  • Christiansen JK, Nielsen JS, Ebersbach T, Valentin-Hansen P, Sogaard-Andersen L, Kallipolitis BH (2006) Identification of small Hfq-binding RNAs in Listeria monocytogenes. RNA 12:1383–1396

    PubMed Central  PubMed  CAS  Google Scholar 

  • Coleman J, Green PJ, Inouye M (1984) The use of RNAs complementary to specific mRNAs to regulate the expression of individual bacterial genes. Cell 37:429–436

    PubMed  CAS  Google Scholar 

  • Cook H, Ussery DW (2013) Sigma factors in a thousand E. coli genomes. Environ Microbiol 15:3121–3129

    PubMed  CAS  Google Scholar 

  • Coornaert A, Lu A, Mandin P, Springer M, Gottesman S, Guillier M (2010) MicA sRNA links the PhoP regulon to cell envelope stress. Mol Microbiol 76:467–479

    PubMed Central  PubMed  CAS  Google Scholar 

  • Coppins RL, Hall KB, Groisman EA (2007) The intricate world of riboswitches. Curr Opin Microbiol 10:176–181

    PubMed Central  PubMed  CAS  Google Scholar 

  • Dahl RH, Zhang F, Alonso-Gutierrez J, Baidoo E, Batth TS, Redding-Johanson AM, Petzold CJ, Mukhopadhyay A, Lee TS, Adams PD, Keasling JD (2013) Engineering dynamic pathway regulation using stress-response promoters. Nat Biotechnol 31:1039–1046

    PubMed  CAS  Google Scholar 

  • Dambach MD, Winkler WC (2009) Expanding roles for metabolite-sensing regulatory RNAs. Curr Opin Microbiol 12:161–169

    PubMed Central  PubMed  CAS  Google Scholar 

  • Davidson ME, Harbaugh SV, Chushak YG, Stone MO, Kelley-Loughnane N (2013) Development of a 2,4-dinitrotoluene-responsive synthetic riboswitch in E. coli cells. ACS Chem Biol 8:234–241

    PubMed  CAS  Google Scholar 

  • Decker KB, Hinton DM (2009) The secret to 6S: regulating RNA polymerase by ribo-sequestration. Mol Microbiol 73:137–140

    PubMed Central  PubMed  CAS  Google Scholar 

  • Desai RP, Papoutsakis ET (1999) Antisense RNA strategies for metabolic engineering of Clostridium acetobutylicum. Appl Environ Microbiol 65:936–945

    PubMed Central  PubMed  CAS  Google Scholar 

  • Desai SK, Gallivan JP (2004) Genetic screens and selections for small molecules based on a synthetic riboswitch that activates protein translation. J Am Chem Soc 126:13247–13254

    PubMed  CAS  Google Scholar 

  • Dietrich JA, McKee AE, Keasling JD (2010) High-throughput metabolic engineering: advances in small-molecule screening and selection. Annu Rev Biochem 79:563–590

    PubMed  CAS  Google Scholar 

  • Ellington AD (2007) What's so great about RNA? ACS Chem Biol 2:445–448

    PubMed  CAS  Google Scholar 

  • Fowler CC, Brown ED, Li YF (2010) Using a riboswitch sensor to examine coenzyme B-12 metabolism and transport in E. coli. Chem Biol 17:756–765

    PubMed  CAS  Google Scholar 

  • Gaida SM, Al-Hinai MA, Indurthi DC, Nicolaou SA, Papoutsakis ET (2013) Synthetic tolerance: three noncoding small RNAs, DsrA, ArcZ and RprA, acting supra-additively against acid stress. Nucleic Acids Res 41:8726–8737

    PubMed Central  PubMed  CAS  Google Scholar 

  • Geissen R, Steuten B, Polen T, Wagner R (2010) E. coli 6S RNA a universal transcriptional regulator within the centre of growth adaptation. RNA Biol 7:564–568

    PubMed  CAS  Google Scholar 

  • Geissmann T, Chevalier C, Cros MJ, Boisset S, Fechter P, Noirot C, Schrenzel J, Francois P, Vandenesch F, Gaspin C, Romby P (2009) A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation. Nucleic Acids Res 37:7239–7257

    PubMed Central  PubMed  CAS  Google Scholar 

  • Gottesman S (2005) Micros for microbes: non-coding regulatory RNAs in bacteria. Trends Genet 21:399–404

    PubMed  CAS  Google Scholar 

  • Gottesman S, Storz G (2011) Bacterial small RNA regulators: versatile roles and rapidly evolving variations. CSH Perspect Biol 3

  • Grosshans H, Filipowicz W (2008) Molecular biology: the expanding world of small RNAs. Nature 451:414–416

    PubMed  CAS  Google Scholar 

  • Grundy FJ, Henkin TM (1998) The S box regulon: a new global transcription termination control system for methionine and cysteine biosynthesis genes in gram-positive bacteria. Mol Microbiol 30:737–749

    PubMed  CAS  Google Scholar 

  • Heinemann M, Sauer U (2010) Systems biology of microbial metabolism. Curr Opin Microbiol 13:337–343

    PubMed  CAS  Google Scholar 

  • Henkin TM (2008) Riboswitch RNAs: using RNA to sense cellular metabolism. Genes Dev 22:3383–3390

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hindley J (1967) Fractionation of 32P-labelled ribonucleic acids on polyacrylamide gels and their characterization by fingerprinting. J Mol Biol 30:125–136

    PubMed  CAS  Google Scholar 

  • Hoe CH, Raabe CA, Rozhdestvensky TS, Tang TH (2013) Bacterial sRNAs: regulation in stress. Int J Med Microbiol 303:217–229

    PubMed  CAS  Google Scholar 

  • Huttenhofer A, Vogel J (2006) Experimental approaches to identify non-coding RNAs. Nucleic Acids Res 34:635–646

    PubMed Central  PubMed  Google Scholar 

  • Irnov I, Sharma CM, Vogel J, Winkler WC (2010) Identification of regulatory RNAs in Bacillus subtilis. Nucleic Acids Res 38:6637–6651

    PubMed Central  PubMed  CAS  Google Scholar 

  • Isaacs FJ, Carr PA, Wang HH, Lajoie MJ, Sterling B, Kraal L, Tolonen AC, Gianoulis TA, Goodman DB, Reppas NB, Emig CJ, Bang D, Hwang SJ, Jewett MC, Jacobson JM, Church GM (2011) Precise manipulation of chromosomes in vivo enables genome-wide codon replacement. Science 333:348–353

    PubMed  CAS  Google Scholar 

  • Jorgensen MG, Thomason MK, Havelund J, Valentin-Hansen P, Storz G (2013) Dual function of the McaS small RNA in controlling biofilm formation. Genes Dev 27:1132–1145

    PubMed Central  PubMed  Google Scholar 

  • Joyce GF (2007) Forty years of in vitro evolution. Angew Chem Int Ed Engl 46:6420–6436

    PubMed  CAS  Google Scholar 

  • Kang Z, Geng YP, Xia YZ, Kang JH, Qi QS (2009) Engineering Escherichia coli for an efficient aerobic fermentation platform. J Biotechnol 144:58–63

    PubMed  CAS  Google Scholar 

  • Kang Z, Wang Q, Zhang HJ, Qi QS (2008) Construction of a stress-induced system in Escherichia coli for efficient polyhydroxyalkanoates production. Appl Microbiol Biotechnol 79:203–208

    PubMed  CAS  Google Scholar 

  • Kang Z, Wang XR, Li YK, Wang Q, Qi QS (2012) Small RNA RyhB as a potential tool used for metabolic engineering in Escherichia coli. Biotechnol Lett 34:527–531

    PubMed  CAS  Google Scholar 

  • Kang Z, Wang Y, Gu PF, Wang Q, Qi QS (2011) Engineering Escherichia coli for efficient production of 5-aminolevulinic acid from glucose. Metab Eng 13:492–498

    PubMed  CAS  Google Scholar 

  • Keasling JD (2012) Synthetic biology and the development of tools for metabolic engineering. Metab Eng 14:189–195

    PubMed  CAS  Google Scholar 

  • Kiga D, Futamura Y, Sakamoto K, Yokoyama S (1998) An RNA aptamer to the xanthine/guanine base with a distinctive mode of purine recognition. Nucleic Acids Res 26:1755–1760

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kim JY, Cha HJ (2003) Down-regulation of acetate pathway through antisense strategy in Escherichia coli: improved foreign protein production. Biotechnol Bioeng 83:841–853

    PubMed  CAS  Google Scholar 

  • Klein DJ, Ferre-D'Amare AR (2006) Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313:1752–1756

    PubMed  CAS  Google Scholar 

  • Klocko AD, Wassarman KM (2009) 6S RNA binding to Esigma(70) requires a positively charged surface of sigma(70) region 4.2. Mol Microbiol 73:152–164

    PubMed Central  PubMed  CAS  Google Scholar 

  • Kohlstedt M, Becker J, Wittmann C (2010) Metabolic fluxes and beyond-systems biology understanding and engineering of microbial metabolism. Appl Microbiol Biotechnol 88:1065–1075

    PubMed  CAS  Google Scholar 

  • Lease RA, Smith D, McDonough K, Belfort M (2004) The small noncoding DsrA RNA is an acid resistance regulator in Escherichia coli. J Bacteriol 186:6179–6185

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lee SY (2011) Metabolic engineering, systems biology and synthetic biology. Microb Biotechnol 4:120–121

    Google Scholar 

  • Levin A, Lis M, Ponty Y, O'Donnell CW, Devadas S, Berger B, Waldispuhl J (2012) A global sampling approach to designing and reengineering RNA secondary structures. Nucleic Acids Res 40:10041–10052

    PubMed Central  PubMed  CAS  Google Scholar 

  • Li FF, Wang Y, Gong K, Wang Q, Liang QF, Qi QS (2013a) Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli. FEMS Microbiol Lett. doi:10.1111/1574-6968.12322

    Google Scholar 

  • Li L, Huang DD, Cheung MK, Nong WY, Huang QL, Kwan HS (2013b) BSRD: a repository for bacterial small regulatory RNA. Nucleic Acids Res 41:233–238

    Google Scholar 

  • Liang JC, Bloom RJ, Smolke CD (2011a) Engineering biological systems with synthetic RNA molecules. Mol Cell 43:915–926

    PubMed Central  PubMed  CAS  Google Scholar 

  • Liang QF, Zhang HJ, Li SN, Qi QS (2011b) Construction of stress-induced metabolic pathway from glucose to 1,3-propanediol in Escherichia coli. Appl Microbiol Biotechnol 89:57–62

    PubMed  CAS  Google Scholar 

  • Lipfert J, Das R, Chu VB, Kudaravalli M, Boyd N, Herschlag D, Doniach S (2007) Structural transitions and thermodynamics of a glycine-dependent riboswitch from Vibrio cholerae. J Mol Biol 365:1393–1406

    PubMed Central  PubMed  CAS  Google Scholar 

  • Livny J, Waldor MK (2007) Identification of small RNAs in diverse bacterial species. Curr Opin Microbiol 10:96–101

    PubMed  CAS  Google Scholar 

  • Mahmood R, Ali I, Husnain T, Riazuddin S (2008) RNA interference: the story of gene silencing in plants and humans. Biotechnol Adv 26:202–209

    Google Scholar 

  • 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

    PubMed Central  PubMed  CAS  Google Scholar 

  • Majdalani N, Hernandez D, Gottesman S (2002) Regulation and mode of action of the second small RNA activator of RpoS translation, RprA. Mol Microbiol 46:813–826

    PubMed  CAS  Google Scholar 

  • Man SA, Cheng RB, Miao CC, Gong QH, Gu YC, Lu XZ, Han F, Yu WG (2011) Artificial trans-encoded small non-coding RNAs specifically silence the selected gene expression in bacteria. Nucleic Acids Res 39:e50

    Google Scholar 

  • Mandal M, Boese B, Barrick JE, Winkler WC, Breaker RR (2003) Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 113:577–586

    PubMed  CAS  Google Scholar 

  • Masse E, Majdalani N, Gottesman S (2003) Regulatory roles for small RNAs in bacteria. Curr Opin Microbiol 6:120–124

    PubMed  CAS  Google Scholar 

  • Mehta A, Sonam S, Gouri I, Loharch S, Sharma DK, Parkesh R (2013) SMMRNA: a database of small molecule modulators of RNA. Nucleic Acids Res. doi:10.1093/nar/gkt976

    Google Scholar 

  • Miranda-Rios J, Navarro M, Soberon M (2001) A conserved RNA structure (thi box) is involved in regulation of thiamin biosynthetic gene expression in bacteria. Proc Natl Acad Sci U S A 98:9736–9741

    PubMed Central  PubMed  CAS  Google Scholar 

  • Mizuno T, Chou MY, Inouye M (1984) A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci U S A 81:1966–1970

    PubMed Central  PubMed  CAS  Google Scholar 

  • Muranaka N, Sharma V, Nomura Y, Yokobayashi Y (2009) An efficient platform for genetic selection and screening of gene switches in Escherichia coli. Nucleic Acids Res 37:e39

    Google Scholar 

  • Na D, Yoo SM, Chung H, Park H, Park JH, Lee SY (2013) Metabolic engineering of Escherichia coli using synthetic small regulatory RNAs. Nat Biotechnol 31:170–174

    PubMed  CAS  Google Scholar 

  • Nakashima N, Tamura T (2009) Conditional gene silencing of multiple genes with antisense RNAs and generation of a mutator strain of Escherichia coli. Nucleic Acids Res 37:e103

    Google Scholar 

  • Nakashima N, Tamura T, Good L (2006) Paired termini stabilize antisense RNAs and enhance conditional gene silencing in Escherichia coli. Nucleic Acids Res 34:e138

    Google Scholar 

  • Negrete A, Majdalani N, Phue JN, Shiloach J (2013) Reducing acetate excretion from E. coli K-12 by over-expressing the small RNA SgrS. N Biotechnol 30:269–273

    PubMed Central  PubMed  CAS  Google Scholar 

  • 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

    PubMed Central  PubMed  Google Scholar 

  • Nielsen J, Pronk JT (2012) Metabolic engineering, synthetic biology and systems biology. FEMS Yeast Res 12:103–103

    PubMed  CAS  Google Scholar 

  • Nou X, Kadner RJ (2000) Adenosylcobalamin inhibits ribosome binding to btuB RNA. Proc Natl Acad Sci U S A 97:7190–7195

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ogawa A (2011) Rational design of artificial riboswitches based on ligand-dependent modulation of internal ribosome entry in wheat germ extract and their applications as label-free biosensors. RNA 17:478–488

    PubMed Central  PubMed  CAS  Google Scholar 

  • Papenfort K, Said N, Welsink T, Lucchini S, Hinton JC, Vogel J (2009) Specific and pleiotropic patterns of mRNA regulation by ArcZ, a conserved, Hfq-dependent small RNA. Mol Microbiol 74:139–158

    PubMed  CAS  Google Scholar 

  • Pfleger BF, Pitera DJ, Smolke CD, Keasling JD (2006) Combinatorial engineering of intergenic regions in operons tunes expression of multiple genes. Nat Biotechnol 24:1027–1032

    PubMed  CAS  Google Scholar 

  • Pichon C, Felden B (2008) Small RNA gene identification and mRNA target predictions in bacteria. Bioinformatics 24:2807–2813

    PubMed  CAS  Google Scholar 

  • Qi L, Lucks JB, Liu CC, Mutalik VK, Arkin AP (2012) Engineering naturally occurring trans-acting non-coding RNAs to sense molecular signals. Nucleic Acids Res 40:5775–5786

    PubMed Central  PubMed  CAS  Google Scholar 

  • Regulski EE, Moy RH, Weinberg Z, Barrick JE, Yao Z, Ruzzo WL, Breaker RR (2008) A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism. Mol Microbiol 68:918–932

    PubMed Central  PubMed  CAS  Google Scholar 

  • Repoila F, Darfeuille F (2009) Small regulatory non-coding RNAs in bacteria: physiology and mechanistic aspects. Biol Cell 101:117–131

    PubMed  CAS  Google Scholar 

  • Rodrigo G, Landrain TE, Jaramillo A (2012) De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells. Proc Natl Acad Sci U S A 109:15271–15276

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rodrigo G, Landrain TE, Shen S, Jaramillo A (2013) A new frontier in synthetic biology: automated design of small RNA devices in bacteria. Trends Genet 29:529–536

    PubMed  CAS  Google Scholar 

  • Romby P, Charpentier E (2010) An overview of RNAs with regulatory functions in gram-positive bacteria. Cell Mol Life Sci 67:217–237

    PubMed  CAS  Google Scholar 

  • Roth A, Winkler WC, Regulski EE, Lee BW, Lim J, Jona I, Barrick JE, Ritwik A, Kim JN, Welz R, Iwata-Reuyl D, Breaker RR (2007) A riboswitch selective for the queuosine precursor preQ1 contains an unusually small aptamer domain. Nat Struct Mol Biol 14:308–317

    PubMed  CAS  Google Scholar 

  • Santos CN, Stephanopoulos G (2008) Combinatorial engineering of microbes for optimizing cellular phenotype. Curr Opin Chem Biol 12:168–176

    PubMed  CAS  Google Scholar 

  • Scheel M, Lutke-Eversloh T (2013) New options to engineer biofuel microbes: development and application of a high-throughput screening system. Metab Eng 17:51–58

    PubMed  CAS  Google Scholar 

  • Serganov A (2009) The long and the short of riboswitches. Curr Opin Struct Biol 19:251–259

    PubMed Central  PubMed  CAS  Google Scholar 

  • Serganov A, Patel DJ (2007) Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. Nat Rev Genet 8:776–790

    PubMed  CAS  Google Scholar 

  • Serganov A, Patel DJ (2012) Metabolite recognition principles and molecular mechanisms underlying riboswitch function. Annu Rev Biophys 41:343–370

    PubMed  CAS  Google Scholar 

  • Seshasayee AS, Bertone P, Fraser GM, Luscombe NM (2006) Transcriptional regulatory networks in bacteria: from input signals to output responses. Curr Opin Microbiol 9:511–519

    PubMed  CAS  Google Scholar 

  • Sharma CM, Vogel J (2009) Experimental approaches for the discovery and characterization of regulatory small RNA. Curr Opin Microbiol 12:536–546

    PubMed  CAS  Google Scholar 

  • Sharma V, Yamamura A, Yokobayashi Y (2012) Engineering artificial small RNAs for conditional gene silencing in Escherichia coli. ACS Synth Biol 1:6–13

    PubMed  CAS  Google Scholar 

  • Sinha J, Reyes SJ, Gallivan JP (2010) Reprogramming bacteria to seek and destroy an herbicide. Nat Chem Biol 6:464–470

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sledjeski DD, Gupta A, Gottesman S (1996) The small RNA, DsrA, is essential for the low temperature expression of RpoS during exponential growth in Escherichia coli. EMBO J 15:3993–4000

    PubMed Central  PubMed  CAS  Google Scholar 

  • Sonnleitner E, Romeo A, Blasi U (2012) Small regulatory RNAs in Pseudomonas aeruginosa. RNA Biol 9:364–371

    PubMed  CAS  Google Scholar 

  • Srivastava R, Cha HJ, Peterson MS, Bentley WE (2000) Antisense downregulation of sigma(32) as a transient metabolic controller in Escherichia coli: effects on yield of active organophosphorus hydrolase. Appl Environ Microbiol 66:4366–4371

    PubMed Central  PubMed  CAS  Google Scholar 

  • Steuten B, Setny P, Zacharias M, Wagner R (2013) Mapping the spatial neighborhood of the regulatory 6S RNA bound to Escherichia coli RNA polymerase holoenzyme. J Mol Biol 425:3649–3661

    PubMed  CAS  Google Scholar 

  • Stevens DC, Conway KR, Pearce N, Villegas-Penaranda LR, Garza AG, Boddy CN (2013) Alternative sigma factor over-expression enables heterologous expression of a type II polyketide biosynthetic pathway in Escherichia coli. PLoS One 8:64858

    Google Scholar 

  • Storz G, Opdyke JA, Zhang A (2004) Controlling mRNA stability and translation with small, noncoding RNAs. Curr Opin Microbiol 7:140–144

    PubMed  CAS  Google Scholar 

  • Sudarsan N, Lee ER, Weinberg Z, Moy RH, Kim JN, Link KH, Breaker RR (2008) Riboswitches in eubacteria sense the second messenger cyclic di-GMP. Science 321:411–413

    PubMed  CAS  Google Scholar 

  • Suess B, Weigand JE (2008) Engineered riboswitches—overview, problems and trends. RNA Biol 5:24–29

    PubMed  CAS  Google Scholar 

  • Tannler S, Zamboni N, Kiraly C, Aymerich S, Sauer U (2008) Screening of Bacillus subtilis transposon mutants with altered riboflavin production. Metab Eng 10:216–226

    PubMed  CAS  Google Scholar 

  • Tjaden B, Goodwin SS, Opdyke JA, Guillier M, Fu DX, Gottesman S, Storz G (2006) Target prediction for small, noncoding RNAs in bacteria. Nucleic Acids Res 34:2791–2802

    PubMed Central  PubMed  CAS  Google Scholar 

  • Topp S, Gallivan JP (2007) Guiding bacteria with small molecules and RNA. J Am Chem Soc 129:6807–6811

    PubMed Central  PubMed  CAS  Google Scholar 

  • Topp S, Reynoso CMK, Seeliger JC, Goldlust IS, Desai SK, Murat D, Shen A, Puri AW, Komeili A, Bertozzi CR, Scott JR, Gallivan JP (2010) Synthetic riboswitches that induce gene expression in diverse bacterial species. Appl Environ Microbiol 76:7881–7884

    PubMed Central  PubMed  CAS  Google Scholar 

  • Trotochaud AE, Wassarman KM (2004) 6S RNA function enhances long-term cell survival. J Bacteriol 186:4978–4985

    PubMed Central  PubMed  CAS  Google Scholar 

  • Vanderpool CK, Gottesman S (2004) Involvement of a novel transcriptional activator and small RNA in post-transcriptional regulation of the glucose phosphoenolpyruvate phosphotransferase system. Mol Microbiol 54:1076–1089

    PubMed  CAS  Google Scholar 

  • Vejnar CE, Blum M, Zdobnov EM (2013) miRmap web: comprehensive microRNA target prediction online. Nucleic Acids Res 41:165–168

    Google Scholar 

  • Vitreschak AG, Rodionov DA, Mironov AA, Gelfand MS (2004) Riboswitches: the oldest mechanism for the regulation of gene expression? Trends Genet 20:44–50

    PubMed  CAS  Google Scholar 

  • Vogel J, Papenfort K (2006) Small non-coding RNAs and the bacterial outer membrane. Curr Opin Microbiol 9:605–611

    PubMed  CAS  Google Scholar 

  • Wachsmuth M, Findeiss S, Weissheimer N, Stadler PF, Morl M (2013) De novo design of a synthetic riboswitch that regulates transcription termination. Nucleic Acids Ress 41:2541–2551

    CAS  Google Scholar 

  • Wadler CS, Vanderpool CK (2007) A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide. Proc Natl Acad Sci U S A 104:20454–20459

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wadler CS, Vanderpool CK (2009) Characterization of homologs of the small RNA SgrS reveals diversity in function. Nucleic Acids Res 37:5477–5485

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature 460:894–898

    PubMed  CAS  Google Scholar 

  • Wang JX, Lee ER, Morales DR, Lim J, Breaker RR (2008) Riboswitches that sense S-adenosylhomocysteine and activate genes involved in coenzyme recycling. Mol Cell 29:691–702

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wassarman KM (2007) 6S RNA: a small RNA regulator of transcription. Curr Opin Microbiol 10:164–168

    PubMed  CAS  Google Scholar 

  • Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S (2001) Identification of novel small RNAs using comparative genomics and microarrays. Gene Dev 15:1637–1651

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wassarman KM, Storz G (2000) 6S RNA regulates E. coli RNA polymerase activity. Cell 101:613–623

    PubMed  CAS  Google Scholar 

  • Waters LS, Storz G (2009) Regulatory RNAs in bacteria. Cell 136:615–628

    PubMed Central  PubMed  CAS  Google Scholar 

  • Win MN, Smolke CD (2007) A modular and extensible RNA-based gene-regulatory platform for engineering cellular function. Proc Natl Acad Sci U S A 104:14283–14288

    PubMed Central  PubMed  CAS  Google Scholar 

  • Winkler W, Nahvi A, Breaker RR (2002a) Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952–956

    PubMed  CAS  Google Scholar 

  • Winkler WC, Cohen-Chalamish S, Breaker RR (2002b) An mRNA structure that controls gene expression by binding FMN. Proc Natl Acad Sci U S A 99:15908–15913

    PubMed Central  PubMed  CAS  Google Scholar 

  • Wurm R, Neusser T, Wagner R (2010) 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products. Biol Chem 391:187–196

    PubMed  CAS  Google Scholar 

  • Yang J, Seo SW, Jang S, Shin SI, Lim CH, Roh TY, Jung GY (2013) Synthetic RNA devices to expedite the evolution of metabolite-producing microbes. Nat Commun 4:1413

    PubMed  Google Scholar 

  • Yoo SM, Na D, Lee SY (2013) Design and use of synthetic regulatory small RNAs to control gene expression in Escherichia coli. Nat Protoc 8:1694–1707

    PubMed  CAS  Google Scholar 

  • Zhang A, Altuvia S, Tiwari A, Argaman L, Hengge-Aronis R, Storz G (1998) The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein. EMBO J 17:6061–6068

    PubMed Central  PubMed  CAS  Google Scholar 

  • Zhao Y, Huang Y, Gong Z, Wang Y, Man J, Xiao Y (2012) Automated and fast building of three-dimensional RNA structures. Sci Rep 2:734

    PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was financially supported by the Major State Basic Research Development Program of China (973 Program, 2012CB720802, 2014CB745103, 2013CB733902, 2013CB733602), the National Natural Science Foundation of China (31200020, 31130043), the National High Technology Research and Development Program of China (863 Program, 2011AA100905), the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT1135), the National Science Foundation for Post-doctoral Scientists of China (2013M540414), the Jiangsu Planned Projects for Postdoctoral Research Funds (1301010B), and the 111 Project.

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Authors and Affiliations

  1. Synergetic Innovation Center of Food Safety and Nutrition, Wuxi, 214122, China

    Zhen Kang, Juan Zhang, Guocheng Du & Jian Chen

  2. The Key Laboratory of Industrial Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Zhen Kang, Chuanzhi Zhang, Junli Zhang, Peng Jin, Juan Zhang, Guocheng Du & Jian Chen

  3. The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi, 214122, China

    Guocheng Du

  4. Synergy Innovation Center of Modern Industrial Fermentation, Wuxi, 214122, China

    Zhen Kang, Juan Zhang, Guocheng Du & Jian Chen

  5. National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, 214122, China

    Jian Chen

  6. Yixing Union Biochemical Co., Ltd., Wuxi, 214203, China

    Zhen Kang

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  1. Zhen Kang
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  2. Chuanzhi Zhang
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  3. Junli Zhang
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  4. Peng Jin
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  5. Juan Zhang
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  6. Guocheng Du
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  7. Jian Chen
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Correspondence to Zhen Kang or Jian Chen.

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Kang, Z., Zhang, C., Zhang, J. et al. Small RNA regulators in bacteria: powerful tools for metabolic engineering and synthetic biology. Appl Microbiol Biotechnol 98, 3413–3424 (2014). https://doi.org/10.1007/s00253-014-5569-y

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  • DOI: https://doi.org/10.1007/s00253-014-5569-y

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