1887

Chapter 6 : The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781683670247/9781683670230_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781683670247/9781683670230_Chap06-2.gif

Abstract:

Bacteria have evolved a wide array of mechanisms to control gene expression in response to environmental changes. These regulatory mechanisms ensure that specific genes are expressed under the appropriate physiological conditions, and they regulate every step of expression from transcription initiation to posttranslational modification and protein stability. The discovery of the T-box mechanism revealed that an uncharged tRNA can interact with an mRNA to regulate expression of the downstream coding region ( ) ( Fig. 1 ). This mechanism was the first of many regulatory systems to be discovered in which -encoded RNA responds directly to a physiological signal to control gene expression through structural rearrangements. Regulatory RNAs of this type, termed riboswitches, have become an intense focus of research, and to date dozens of riboswitch classes that respond to various signals have been identified and characterized, including those that respond to temperature, pH, and metabolites such as enzyme cofactors, amino acids, and nucleotides ( ).

Citation: Kreuzer K, Henkin T. 2019. The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation, p 89-100. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0028-2018
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

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.

Citation: Kreuzer K, Henkin T. 2019. The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation, p 89-100. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0028-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
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.

Citation: Kreuzer K, Henkin T. 2019. The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation, p 89-100. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0028-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
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 (PDB ID: 4MGN).

Citation: Kreuzer K, Henkin T. 2019. The T-Box Riboswitch: tRNA as an Effector to Modulate Gene Regulation, p 89-100. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0028-2018
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781683670247.chap6
1. Grundy FJ,, Henkin TM . 1993. tRNA as a positive regulator of transcription antitermination in B. subtilis. Cell 74 : 475 482.[CrossRef][PubMed]
2. Sherwood AV,, Henkin TM . 2016. Riboswitch-mediated gene regulation: novel RNA architechtures dictate gene expression responses. Annu Rev Microbiol 70 : 361 374.[CrossRef]
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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][PubMed]
8. Liu LC,, Grundy FJ,, Henkin TM . 2015. Non-conserved residues in Clostridium acetobutylicum tRNA Ala contribute to tRNA tuning for efficient antitermination of the alaS T box riboswitch. Life (Basel) 5 : 1567 1582.[CrossRef]
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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][PubMed]
26. Zhang J,, Ferré-D’Amaré AR . 2016. The tRNA elbow in structure, recognition and evolution. Life (Basel) 6 : 3.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][PubMed]
30. Yousef MR,, Grundy FJ,, Henkin TM . 2003. tRNA requirements for glyQS antitermination: a new twist on tRNA. RNA 9 : 1148 1156.[CrossRef][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.[CrossRef][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.[CrossRef]
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.[CrossRef][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.[CrossRef][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 tRNA Gly. FEBS Lett 587 : 3495 3499.[CrossRef][PubMed]
36. Schroeder KT,, McPhee SA,, Ouellet J,, Lilley DMJ . 2010. A structural database for k-turn motifs in RNA. RNA 16 : 1463 1468.[CrossRef][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.[CrossRef][PubMed]
38. Lilley DM . 2014. The K-turn motif in riboswitches and other RNA species. Biochim Biophys Acta 1839 : 995 1004.[CrossRef][PubMed]
39. Chang AT,, Nikonowicz EP . 2012. Solution nuclear magnetic resonance analyses of the anticodon arms of proteinogenic and nonproteinogenic tRNA Gly. Biochemistry 51 : 3662 3674.[CrossRef][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.[CrossRef][PubMed]
41. Zhang J,, Ferré-D’Amaré AR . 2015. Structure and mechanism of the T-box riboswitches. Wiley Interdiscip Rev RNA 6 : 419 433.[CrossRef][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.[CrossRef][PubMed]
43. Chetnani B,, Mondragón A . 2017. Molecular envelope and atomic model of an anti-terminated glyQS T-box regulator in complex with tRNA Gly. Nucleic Acids Res 45 : 8079 8090.[CrossRef][PubMed]
44. Thomas JR,, Hergenrother PJ . 2008. Targeting RNA twith small molecules. Chem Rev 108 : 1171 1224.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][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.[CrossRef][PubMed]

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