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The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation

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  • Authors: Kiel D. Kreuzer1, Tina M. Henkin3
  • Editors: Gisela Storz4, Kai Papenfort5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology and Center for RNA Biology; 2: Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210; 3: Department of Microbiology and Center for RNA Biology; 4: Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; 5: Department of Biology I, Microbiology, LMU Munich, Martinsried, Germany
  • Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0028-2018
  • Received 19 February 2018 Accepted 08 May 2018 Published 27 July 2018
  • Tina M. Henkin, [email protected]
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  • Abstract:

    The T-box riboswitch is a unique, RNA-based regulatory mechanism that modulates expression of a wide variety of amino acid-related genes, predominantly in . RNAs of this class selectively bind a specific cognate tRNA, utilizing recognition of the tRNA anticodon and other tRNA features. The riboswitch monitors the aminoacylation status of the tRNA to induce expression of the regulated downstream gene(s) at the level of transcription antitermination or derepression of translation initiation in response to reduced tRNA charging via stabilization of an antiterminator or antisequestrator. Recent biochemical and structural studies have revealed new features of tRNA recognition that extend beyond the initially identified Watson-Crick base-pairing of a codon-like sequence in the riboswitch with the tRNA anticodon, and residues in the antiterminator or antisequestrator with the tRNA acceptor end. These studies have revealed new tRNA contacts and new modes of riboswitch function and ligand recognition that expand our understanding of RNA-RNA recognition and the biological roles of tRNA.

  • Citation: Kreuzer K, Henkin T. 2018. The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation. Microbiol Spectrum 6(4):RWR-0028-2018. doi:10.1128/microbiolspec.RWR-0028-2018.

References

1. Grundy FJ, Henkin TM. 1993. tRNA as a positive regulator of transcription antitermination in B. subtilis. Cell 74:475–482. http://dx.doi.org/10.1016/0092-8674(93)80049-K. [PubMed]
2. Sherwood AV, Henkin TM. 2016. Riboswitch-mediated gene regulation: novel RNA architechtures dictate gene expression responses. Annu Rev Microbiol 70:361–374. https://doi.org/10.1146/annurev-micro-091014-104306.
3. Giegé R, Jühling F, Pütz J, Stadler P, Sauter C, Florentz C. 2012. Structure of transfer RNAs: similarity and variability. Wiley Interdiscip Rev RNA 3:37–61. http://dx.doi.org/10.1002/wrna.103. [PubMed]
4. Henkin TM, Glass BL, Grundy FJ. 1992. Analysis of the Bacillus subtilis tyrS gene: conservation of a regulatory sequence in multiple tRNA synthetase genes. J Bacteriol 174:1299–1306. http://dx.doi.org/10.1128/jb.174.4.1299-1306.1992. [PubMed]
5. Grundy FJ, Rollins SM, Henkin TM. 1994. Interaction between the acceptor end of tRNA and the T box stimulates antitermination in the Bacillus subtilis tyrS gene: a new role for the discriminator base. J Bacteriol 176:4518–4526. http://dx.doi.org/10.1128/jb.176.15.4518-4526.1994. [PubMed]
6. Grundy FJ, Yousef MR, Henkin TM. 2005. Monitoring uncharged tRNA during transcription of the Bacillus subtilis glyQS gene. J Mol Biol 346:73–81. http://dx.doi.org/10.1016/j.jmb.2004.11.051. [PubMed]
7. Grundy FJ, Winkler WC, Henkin TM. 2002. tRNA-mediated transcription antitermination in vitro: codon-anticodon pairing independent of the ribosome. Proc Natl Acad Sci U S A 99:11121–11126. http://dx.doi.org/10.1073/pnas.162366799. [PubMed]
8. Liu LC, Grundy FJ, Henkin TM. 2015. Non-conserved residues in Clostridium acetobutylicum tRNAAla contribute to tRNA tuning for efficient antitermination of the alaS T box riboswitch. Life (Basel) 5:1567–1582. http://dx.doi.org/10.3390/life5041567.
9. Sherwood AV, Grundy FJ, Henkin TM. 2015. T box riboswitches in Actinobacteria: translational regulation via novel tRNA interactions. Proc Natl Acad Sci U S A 112:1113–1118. http://dx.doi.org/10.1073/pnas.1424175112. [PubMed]
10. Gutiérrez-Preciado A, Henkin TM, Grundy FJ, Yanofsky C, Merino E. 2009. Biochemical features and functional implications of the RNA-based T-box regulatory mechanism. Microbiol Mol Biol Rev 73:36–61. http://dx.doi.org/10.1128/MMBR.00026-08. [PubMed]
11. Grigg JC, Ke A. 2013. Structural determinants for geometry and information decoding of tRNA by T box leader RNA. Structure 21:2025–2032. http://dx.doi.org/10.1016/j.str.2013.09.001. [PubMed]
12. Zhang J, Ferré-D’Amaré AR. 2013. Co-crystal structure of a T-box riboswitch Stem I domain in complex with its cognate tRNA. Nature 500:363–366. http://dx.doi.org/10.1038/nature12440. [PubMed]
13. Winkler WC, Grundy FJ, Murphy BA, Henkin TM. 2001. The GA motif: an RNA element common to bacterial antitermination systems, rRNA, and eukaryotic RNAs. RNA 7:1165–1172. http://dx.doi.org/10.1017/S1355838201002370. [PubMed]
14. Klein DJ, Schmeing TM, Moore PB, Steitz TA. 2001. The kink-turn: a new RNA secondary structure motif. EMBO J 20:4214–4221. http://dx.doi.org/10.1093/emboj/20.15.4214. [PubMed]
15. Rollins SM, Grundy FJ, Henkin TM. 1997. Analysis of cis-acting sequence and structural elements required for antitermination of the Bacillus subtilis tyrS gene. Mol Microbiol 25:411–421. http://dx.doi.org/10.1046/j.1365-2958.1997.4851839.x. [PubMed]
16. Vitreschak AG, Mironov AA, Lyubetsky VA, Gelfand MS. 2008. Comparative genomic analysis of T-box regulatory systems in bacteria. RNA 14:717–735. http://dx.doi.org/10.1261/rna.819308. [PubMed]
17. Grundy FJ, Hodil SE, Rollins SM, Henkin TM. 1997. Specificity of tRNA-mRNA interactions in Bacillus subtilis tyrS antitermination. J Bacteriol 179:2587–2594. http://dx.doi.org/10.1128/jb.179.8.2587-2594.1997. [PubMed]
18. Marta PT, Ladner RD, Grandoni JA. 1996. A CUC triplet confers leucine-dependent regulation of the Bacillus subtilis ilv-leu operon. J Bacteriol 178:2150–2153. http://dx.doi.org/10.1128/jb.178.7.2150-2153.1996. [PubMed]
19. Luo D, Leautey J, Grunberg-Manago M, Putzer H. 1997. Structure and regulation of expression of the Bacillus subtilis valyl-tRNA synthetase gene. J Bacteriol 179:2472–2478. http://dx.doi.org/10.1128/jb.179.8.2472-2478.1997. [PubMed]
20. Brill J, Hoffmann T, Putzer H, Bremer E. 2011. T-box-mediated control of the anabolic proline biosynthetic genes of Bacillus subtilis. Microbiology 157:977–987. http://dx.doi.org/10.1099/mic.0.047357-0. [PubMed]
21. Saad NY, Stamatopoulou V, Brayé M, Drainas D, Stathopoulos C, Becker HD. 2013. Two-codon T-box riboswitch binding two tRNAs. Proc Natl Acad Sci U S A 110:12756–12761. http://dx.doi.org/10.1073/pnas.1304307110. [PubMed]
22. Caserta E, Liu LC, Grundy FJ, Henkin TM. 2015. Codon-anticodon recognition in the Bacillus subtilis glyQS T box riboswitch: RNA-dependent codon selection outside the ribosome. J Biol Chem 290:23336–23347. http://dx.doi.org/10.1074/jbc.M115.673236. [PubMed]
23. Gerdeman MS, Henkin TM, Hines JV. 2002. In vitro structure-function studies of the Bacillus subtilis tyrS mRNA antiterminator: evidence for factor-independent tRNA acceptor stem binding specificity. Nucleic Acids Res 30:1065–1072. http://dx.doi.org/10.1093/nar/30.4.1065. [PubMed]
24. Zhang J, Ferré-D’Amaré AR. 2014. Direct evaluation of tRNA aminoacylation status by the T-box riboswitch using tRNA-mRNA stacking and steric readout. Mol Cell 55:148–155. http://dx.doi.org/10.1016/j.molcel.2014.05.017. [PubMed]
25. Grigg JC, Chen Y, Grundy FJ, Henkin TM, Pollack L, Ke A. 2013. T box RNA decodes both the information content and geometry of tRNA to affect gene expression. Proc Natl Acad Sci U S A 110:7240–7245. http://dx.doi.org/10.1073/pnas.1222214110. [PubMed]
26. Zhang J, Ferré-D’Amaré AR. 2016. The tRNA elbow in structure, recognition and evolution. Life (Basel) 6:3. http://dx.doi.org/10.3390/life6010003. [PubMed]
27. Lehmann J, Jossinet F, Gautheret D. 2013. A universal RNA structural motif docking the elbow of tRNA in the ribosome, RNAse P and T-box leaders. Nucleic Acids Res 41:5494–5502. http://dx.doi.org/10.1093/nar/gkt219. [PubMed]
28. Trabuco LG, Schreiner E, Eargle J, Cornish P, Ha T, Luthey-Schulten Z, Schulten K. 2010. The role of L1 stalk-tRNA interaction in the ribosome elongation cycle. J Mol Biol 402:741–760. http://dx.doi.org/10.1016/j.jmb.2010.07.056. [PubMed]
29. Reiter NJ, Osterman A, Torres-Larios A, Swinger KK, Pan T, Mondragón A. 2010. Structure of a bacterial ribonuclease P holoenzyme in complex with tRNA. Nature 468:784–789. http://dx.doi.org/10.1038/nature09516. [PubMed]
30. Yousef MR, Grundy FJ, Henkin TM. 2003. tRNA requirements for glyQS antitermination: a new twist on tRNA. RNA 9:1148–1156. http://dx.doi.org/10.1261/rna.5540203. [PubMed]
31. Sherwood AV, Frandsen JK, Grundy FJ, Henkin TM. 2018. New tRNA contacts facilitate ligand binding in a Mycobacterium smegmatis T box riboswitch. Proc Natl Acad Sci U S A 115:3894–3899. http://dx.doi.org/10.1073/pnas.1721254115. [PubMed]
32. Gerdeman MS, Henkin TM, Hines JV. 2003. Solution structure of the Bacillus subtilis T-box antiterminator RNA: seven nucleotide bulge characterized by stacking and flexibility. J Mol Biol 326:189–201. http://dx.doi.org/10.1016/S0022-2836(02)01339-6.
33. Means JA, Simson CM, Zhou S, Rachford AA, Rack JJ, Hines JV. 2009. Fluorescence probing of T box antiterminator RNA: insights into riboswitch discernment of the tRNA discriminator base. Biochem Biophys Res Commun 389:616–621. http://dx.doi.org/10.1016/j.bbrc.2009.09.037. [PubMed]
34. Wang J, Henkin TM, Nikonowicz EP. 2010. NMR structure and dynamics of the Specifier Loop domain from the Bacillus subtilis tyrS T box leader RNA. Nucleic Acids Res 38:3388–3398. http://dx.doi.org/10.1093/nar/gkq020. [PubMed]
35. Chang AT, Nikonowicz EP. 2013. Solution NMR determination of hydrogen bonding and base pairing between the glyQS T box riboswitch Specifier domain and the anticodon loop of tRNAGly. FEBS Lett 587:3495–3499. http://dx.doi.org/10.1016/j.febslet.2013.09.003. [PubMed]
36. Schroeder KT, McPhee SA, Ouellet J, Lilley DMJ. 2010. A structural database for k-turn motifs in RNA. RNA 16:1463–1468. http://dx.doi.org/10.1261/rna.2207910. [PubMed]
37. Wang J, Nikonowicz EP. 2011. Solution structure of the K-turn and Specifier Loop domains from the Bacillus subtilis tyrS T-box leader RNA. J Mol Biol 408:99–117. http://dx.doi.org/10.1016/j.jmb.2011.02.014. [PubMed]
38. Lilley DM. 2014. The K-turn motif in riboswitches and other RNA species. Biochim Biophys Acta 1839:995–1004. http://dx.doi.org/10.1016/j.bbagrm.2014.04.020. [PubMed]
39. Chang AT, Nikonowicz EP. 2012. Solution nuclear magnetic resonance analyses of the anticodon arms of proteinogenic and nonproteinogenic tRNAGly. Biochemistry 51:3662–3674. http://dx.doi.org/10.1021/bi201900j. [PubMed]
40. Dunkle JA, Wang L, Feldman MB, Pulk A, Chen VB, Kapral GJ, Noeske J, Richardson JS, Blanchard SC, Cate JH. 2011. Structures of the bacterial ribosome in classical and hybrid states of tRNA binding. Science 332:981–984. http://dx.doi.org/10.1126/science.1202692. [PubMed]
41. Zhang J, Ferré-D’Amaré AR. 2015. Structure and mechanism of the T-box riboswitches. Wiley Interdiscip Rev RNA 6:419–433. http://dx.doi.org/10.1002/wrna.1285. [PubMed]
42. Fang X, Michnicka M, Zhang Y, Wang YX, Nikonowicz EP. 2017. Capture and release of tRNA by the T-loop receptor in the function of the T-box riboswitch. Biochemistry 56:3549–3558. http://dx.doi.org/10.1021/acs.biochem.7b00284. [PubMed]
43. Chetnani B, Mondragón A. 2017. Molecular envelope and atomic model of an anti-terminated glyQS T-box regulator in complex with tRNAGly. Nucleic Acids Res 45:8079–8090. http://dx.doi.org/10.1093/nar/gkx451. [PubMed]
44. Thomas JR, Hergenrother PJ. 2008. Targeting RNA with small molecules. Chem Rev 108:1171–1224. http://dx.doi.org/10.1021/cr0681546. [PubMed]
45. Zhou S, Means JA, Acquaah-Harrison G, Bergmeier SC, Hines JV. 2012. Characterization of a 1,4-disubstituted 1,2,3-triazole binding to T box antiterminator RNA. Bioorg Med Chem 20:1298–1302. http://dx.doi.org/10.1016/j.bmc.2011.12.017. [PubMed]
46. Means JA, Hines JV. 2005. Fluorescence resonance energy transfer studies of aminoglycoside binding to a T box antiterminator RNA. Bioorg Med Chem Lett 15:2169–2172. http://dx.doi.org/10.1016/j.bmcl.2005.02.007. [PubMed]
47. Orac CM, Zhou S, Means JA, Boehm D, Bergmeier SC, Hines JV. 2011. Synthesis and stereospecificity of 4,5-disubstituted oxazolidinone ligands binding to T-box riboswitch RNA. J Med Chem 54:6786–6795. http://dx.doi.org/10.1021/jm2006904. [PubMed]
48. Zhou S, Acquaah-Harrison G, Bergmeier SC, Hines JV. 2011. Anisotropy studies of tRNA-T box antiterminator RNA complex in the presence of 1,4-disubstituted 1,2,3-triazoles. Bioorg Med Chem Lett 21:7059–7063. http://dx.doi.org/10.1016/j.bmcl.2011.09.095. [PubMed]
49. Stamatopoulou V, Apostolidi M, Li S, Lamprinou K, Papakyriakou A, Zhang J, Stathopoulos C. 2017. Direct modulation of T-box riboswitch-controlled transcription by protein synthesis inhibitors. Nucleic Acids Res 45:10242–10258. http://dx.doi.org/10.1093/nar/gkx663. [PubMed]
50. Dar D, Shamir M, Mellin JR, Koutero M, Stern-Ginossar N, Cossart P, Sorek R. 2016. Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria. Science 352:aad9822. http://dx.doi.org/10.1126/science.aad9822. [PubMed]
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/content/journal/microbiolspec/10.1128/microbiolspec.RWR-0028-2018
2018-07-27
2018-08-16

Abstract:

The T-box riboswitch is a unique, RNA-based regulatory mechanism that modulates expression of a wide variety of amino acid-related genes, predominantly in . RNAs of this class selectively bind a specific cognate tRNA, utilizing recognition of the tRNA anticodon and other tRNA features. The riboswitch monitors the aminoacylation status of the tRNA to induce expression of the regulated downstream gene(s) at the level of transcription antitermination or derepression of translation initiation in response to reduced tRNA charging via stabilization of an antiterminator or antisequestrator. Recent biochemical and structural studies have revealed new features of tRNA recognition that extend beyond the initially identified Watson-Crick base-pairing of a codon-like sequence in the riboswitch with the tRNA anticodon, and residues in the antiterminator or antisequestrator with the tRNA acceptor end. These studies have revealed new tRNA contacts and new modes of riboswitch function and ligand recognition that expand our understanding of RNA-RNA recognition and the biological roles of tRNA.

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Figures

Image of FIGURE 1
FIGURE 1

The T-box mechanism. (A) tRNA interacts with Stem I of the T-box leader RNA at two locations. The tRNA anticodon base-pairs with the Specifier Sequence (green), and the tRNA elbow stacks with the Stem I platform (orange), which is formed by interactions between conserved sequence motifs. The presence of an amino acid (AA) at the 3′ end of a charged tRNA blocks the base-pairing interaction with a bulge in the antiterminator helix. The terminator helix forms and transcription terminates, which turns gene expression off. (B) Uncharged tRNA also interacts with the Specifier Sequence and Stem I platform, and the acceptor arm base-pairs with a bulge in the antiterminator helix (cyan). The stabilization of the antiterminator prevents formation of the competing terminator helix, and RNA polymerase continues to transcribe the downstream coding sequence.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0028-2018
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Image of FIGURE 2
FIGURE 2

leader RNA and tRNA secondary structure. (A) The sequence is numbered from the transcriptional start site to the end of the transcriptional terminator element. Conserved structural domains are labeled, including Stems I, II, IIA/B, and III and mutually exclusive terminator and antiterminator helices. The Stem IIB pseudoknot interaction is shown in magenta. The Specifier Sequence in the Specifier Loop and residues in the antiterminator bulge that base-pair with tRNA are shown in green and cyan, respectively. The orange sequences in the AG bulge and Stem I terminal loop interact to form the Stem I platform, which contacts the tRNA elbow. The red- and blue-labeled sequences interact to form the antiterminator element shown above the terminator conformation. The antiterminator is composed of helices A1 and A2. (B) Cloverleaf structure of tRNA. The anticodon sequence is shown in green, and the nucleotides in the acceptor arm that base-pair with the antiterminator bulge are shown in cyan. The orange residues in the D-loop and T-loop (G19 and C56) interact to form the outermost tertiary interaction of the elbow and stack with the Stem I platform.

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0028-2018
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Image of FIGURE 3
FIGURE 3

Cocrystal structure of the Stem I-tRNA complex. The Stem I (gray) is bound to tRNA (purple). The Specifier Sequence-anticodon interaction is shown in green, and the Stem I platform that stacks with the tRNA elbow is shown in orange. Data from reference 11 (PDB ID: 4MGN).

Source: microbiolspec July 2018 vol. 6 no. 4 doi:10.1128/microbiolspec.RWR-0028-2018
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