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Annual Review of Microbiology

Volume 75, 2021

Transcriptional Pausing as a Mediator of Bacterial Gene Regulation

Abstract

Cellular life depends on transcription of DNA by RNA polymerase to express genetic information. RNA polymerase has evolved not just to read information from DNA and write it to RNA but also to sense and process information from the cellular and extracellular environments. Much of this information processing occurs during transcript elongation, when transcriptional pausing enables regulatory decisions. Transcriptional pauses halt RNA polymerase in response to DNA and RNA sequences and structures at locations and times that help coordinate interactions with small molecules and transcription factors important for regulation. Four classes of transcriptional pause signals are now evident after decades of study: elemental pauses, backtrack pauses, hairpin-stabilized pauses, and regulator-stabilized pauses. In this review, I describe current understanding of the molecular mechanisms of these four classes of pause signals, remaining questions about how RNA polymerase responds to pause signals, and the many exciting directions now open to understand pausing and the regulation of transcript elongation on a genome-wide scale.

Keyword(s): backtracking, elemental pause, gene regulation, pausing, RNA polymerase, RNA structure, swiveling, transcription
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2021-10-08
2024-04-19
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Literature Cited

  1. 1. 
    Abdelkareem M, Saint-Andre C, Takacs M, Papai G, Crucifix C et al. 2019. Structural basis of transcription: RNA polymerase backtracking and its reactivation. Mol. Cell 75:298–309.e4
     [Google Scholar]
  2. 2. 
    Antson AA, Dodson EJ, Dodson G, Greaves RB, Chen X, Gollnick P. 1999. Structure of the trp RNA-binding attenuation protein, TRAP, bound to RNA. Nature 401:235–42
     [Google Scholar]
  3. 3. 
    Artsimovitch I, Knauer SH. 2019. Ancient transcription factors in the news. mBio 10:e01547-18
     [Google Scholar]
  4. 4. 
    Artsimovitch I, Landick R. 1998. Interaction of a nascent RNA structure with RNA polymerase is required for hairpin-dependent transcriptional pausing but not for transcript release. Genes Dev 12:3110–22
     [Google Scholar]
  5. 5. 
    Artsimovitch I, Landick R 2000. Pausing by bacterial RNA polymerase is mediated by mechanistically distinct classes of signals. PNAS 97:7090–95
     [Google Scholar]
  6. 6. 
    Artsimovitch I, Landick R. 2002. The transcriptional regulator RfaH stimulates RNA chain synthesis after recruitment to elongation complexes by the exposed nontemplate DNA strand. Cell 109:193–203
     [Google Scholar]
  7. 7. 
    Bai L, Shundrovsky A, Wang MD. 2004. Sequence-dependent kinetic model for transcription elongation by RNA polymerase. J. Mol. Biol. 344:335–49
     [Google Scholar]
  8. 8. 
    Bar-Nahum G, Epshtein V, Ruckenstein A, Rafikov R, Mustaev A, Nudler E. 2005. A ratchet mechanism of transcription elongation and its control. Cell 120:183–93
     [Google Scholar]
  9. 9. 
    Bar-Nahum G, Nudler E. 2001. Isolation and characterization of σ70-retaining transcription elongation complexes from Escherichia coli. Cell 106:443–51
     [Google Scholar]
  10. 10. 
    Belogurov GA, Artsimovitch I. 2015. Regulation of transcript elongation. Annu. Rev. Microbiol. 69:49–69
     [Google Scholar]
  11. 11. 
    Belogurov GA, Artsimovitch I. 2019. The mechanisms of substrate selection, catalysis, and translocation by the elongating RNA polymerase. J. Mol. Biol. 431:3975–4006
     [Google Scholar]
  12. 12. 
    Belogurov GA, Vassylyeva MN, Svetlov V, Klyuyev S, Grishin NV et al. 2007. Structural basis for converting a general transcription factor into an operon-specific virulence regulator. Mol. Cell 26:117–29
     [Google Scholar]
  13. 13. 
    Bird JG, Strobel EJ, Roberts JW. 2016. A universal transcription pause sequence is an element of initiation factor σ70-dependent pausing. Nucleic Acids Res 44:6732–40
     [Google Scholar]
  14. 14. 
    Bochkareva A, Yuzenkova Y, Tadigotla VR, Zenkin N. 2012. Factor-independent transcription pausing caused by recognition of the RNA-DNA hybrid sequence. EMBO J 31:630–39
     [Google Scholar]
  15. 15. 
    Boudreau BA, Hron DR, Qin L, van der Valk RA, Kotlajich MV et al. 2018. StpA and Hha stimulate pausing by RNA polymerase by promoting DNA-DNA bridging of H-NS filaments. Nucleic Acids Res 46:5525–46
     [Google Scholar]
  16. 16. 
    Brown A, Fernandez IS, Gordiyenko Y, Ramakrishnan V. 2016. Ribosome-dependent activation of stringent control. Nature 534:277–80
     [Google Scholar]
  17. 17. 
    Burman BM, Knauer SH, Sevostyanova A, Schweimer K, Mooney RA et al. 2012. An alpha helix to beta barrel domain switch transforms the transcription factor RfaH into a translation factor. Cell 150:291–303
     [Google Scholar]
  18. 18. 
    Burns CM, Richardson LV, Richardson JP. 1998. Combinatorial effects of NusA and NusG on transcription elongation and Rho-dependent termination in Escherichia coli. J. Mol. Biol. 278:307–16
     [Google Scholar]
  19. 19. 
    Cantos R, Labella JI, Espinosa J, Contreras A. 2019. The nitrogen regulator PipX acts in cis to prevent operon polarity. Environ. Microbiol. Rep. 11:495–507
     [Google Scholar]
  20. 20. 
    Chamberlin M, Berg P 1962. Deoxyribonucleic acid-directed synthesis of ribonucleic acid by an enzyme from Escherichia coli. PNAS 48:81–94
     [Google Scholar]
  21. 21. 
    Chan C, Landick R. 1997. Effects of neutral salts of transcript elongation and pausing suggest the his leader pause RNA hairpin interacts with an easily disordered region of RNA polymerase. J. Mol. Biol. 268:37–53
     [Google Scholar]
  22. 22. 
    Chan C, Wang D, Landick R. 1997. Spacing from the transcript 3′ end determines whether a nascent RNA hairpin interacts with RNA polymerase to prolong pausing or triggers termination. J. Mol. Biol. 268:54–68
     [Google Scholar]
  23. 23. 
    Chan CL, Landick R. 1989. The Salmonella typhimurium his operon leader region contains an RNA hairpin-dependent transcription pause site: mechanistic implications of the effect on pausing of altered RNA hairpins. J. Biol. Chem. 264:20796–804
     [Google Scholar]
  24. 24. 
    Chan CL, Landick R. 1993. Dissection of the his leader pause site by base substitution reveals a multipartite signal that includes a pause RNA hairpin. J. Mol. Biol. 233:25–42
     [Google Scholar]
  25. 25. 
    Chatzidaki-Livanis M, Coyne MJ, Comstock LE. 2009. A family of transcriptional antitermination factors necessary for synthesis of the capsular polysaccharides of Bacteroides fragilis. J. Bacteriol. 191:7288–95
     [Google Scholar]
  26. 26. 
    Chauvier A, Nadon JF, Grondin JP, Lamontagne AM, Lafontaine DA. 2019. Role of a hairpin-stabilized pause in the Escherichia coli thiC riboswitch function. RNA Biol 16:1066–73
     [Google Scholar]
  27. 27. 
    Chen J, Boyaci H, Campbell EA. 2021. Diverse and unified mechanisms of transcription initiation in bacteria. Nat. Rev. Microbiol. 19:95–109
     [Google Scholar]
  28. 28. 
    Chen M, Fredrick K 2018. Measures of single- versus multiple-round translation argue against a mechanism to ensure coupling of transcription and translation. PNAS 115:10774–79
     [Google Scholar]
  29. 29. 
    Cheng B, Zhu CX, Ji C, Ahumada A, Tse-Dinh YC. 2003. Direct interaction between Escherichia coli RNA polymerase and the zinc ribbon domains of DNA topoisomerase I. J. Biol. Chem. 278:30705–10
     [Google Scholar]
  30. 30. 
    Churchman LS, Weissman JS. 2011. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 469:368–73
     [Google Scholar]
  31. 31. 
    Conrad T, Frazier M, Joyce A, Cho B, Knight E et al. 2010. RNA polymerase mutants found through adaptive evolution re-program Escherichia coli for optimal growth in minimal media. PNAS 107:20500–5
     [Google Scholar]
  32. 32. 
    Dame RT, Rashid FM, Grainger DC. 2020. Chromosome organization in bacteria: mechanistic insights into genome structure and function. Nat. Rev. Genet. 21:227–42
     [Google Scholar]
  33. 33. 
    Dangkulwanich M, Ishibashi T, Liu S, Kireeva ML, Lubkowska L et al. 2013. Complete dissection of transcription elongation reveals slow translocation of RNA polymerase II in a linear ratchet mechanism. eLife 2:e00971
     [Google Scholar]
  34. 34. 
    Darst SA, Opalka N, Chacon P, Polyakov A, Richter C et al. 2002. Conformational flexibility of bacterial RNA polymerase. PNAS 99:4296–301
     [Google Scholar]
  35. 35. 
    Deighan P, Pukhrambam C, Nickels BE, Hochschild A. 2011. Initial transcribed region sequences influence the composition and functional properties of the bacterial elongation complex. Genes Dev 25:77–88
     [Google Scholar]
  36. 36. 
    Donahue JP, Turnbough CL Jr. 1994. Nucleotide-specific transcriptional pausing in the pyrBI leader region of Escherichia coli K-12. J. Biol. Chem. 269:18185–91
     [Google Scholar]
  37. 37. 
    Drolet M. 2006. Growth inhibition mediated by excess negative supercoiling: the interplay between transcription elongation, R-loop formation and DNA topology. Mol. Microbiol. 59:723–30
     [Google Scholar]
  38. 38. 
    Duchi D, Mazumder A, Malinen AM, Ebright RH, Kapanidis AN. 2018. The RNA polymerase clamp interconverts dynamically among three states and is stabilized in a partly closed state by ppGpp. Nucleic Acids Res 46:7284–95
     [Google Scholar]
  39. 39. 
    Epshtein V, Toulme F, Rahmouni AR, Borukhov S, Nudler E. 2003. Transcription through the roadblocks: the role of RNA polymerase cooperation. EMBO J 22:4719–27
     [Google Scholar]
  40. 40. 
    Erijman L, Clegg RM. 1998. Reversible stalling of transcription elongation complexes by high pressure. Biophys. J. 75:453–62
     [Google Scholar]
  41. 41. 
    Farnsworth KD, Nelson J, Gershenson C. 2013. Living is information processing: from molecules to global systems. Acta Biotheor 61:203–22
     [Google Scholar]
  42. 42. 
    Gabizon R, Lee A, Vahedian-Movahed H, Ebright RH, Bustamante CJ. 2018. Pause sequences facilitate entry into long-lived paused states by reducing RNA polymerase transcription rates. Nat. Commun. 9:2930
     [Google Scholar]
  43. 43. 
    Gajos M, Jasnovidova O, van Bommel A, Freier S, Vingron M, Mayer A. 2021. Conserved DNA sequence features underlie pervasive RNA polymerase pausing. Nucleic Acids Res 49:4402–20
     [Google Scholar]
  44. 44. 
    Galburt EA, Grill SW, Wiedmann A, Lubkowska L, Choy J et al. 2007. Backtracking determines the force sensitivity of RNAP II in a factor-dependent manner. Nature 446:820–23
     [Google Scholar]
  45. 45. 
    Goldman SR, Nair NU, Wells CD, Nickels BE, Hochschild A 2015. The primary sigma factor in Escherichia coli can access the transcription elongation complex from solution in vivo. eLife 4:e10514
     [Google Scholar]
  46. 46. 
    Goodson JR, Klupt S, Zhang C, Straight P, Winkler WC. 2017. LoaP is a broadly conserved antiterminator protein that regulates antibiotic gene clusters in Bacillus amyloliquefaciens. Nat. Microbiol. 2:17003
     [Google Scholar]
  47. 47. 
    Goodson JR, Winkler WC. 2018. Processive antitermination. Microbiol. Spectr 6: https://doi.org/10.1128/microbiolspec.RWR-0031-2018
    [Crossref] [Google Scholar]
  48. 48. 
    Gourse RL, Chen AY, Gopalkrishnan S, Sanchez-Vazquez P, Myers A, Ross W. 2018. Transcriptional responses to ppGpp and DksA. Annu. Rev. Microbiol. 72:163–84
     [Google Scholar]
  49. 49. 
    Gralla JD, Vargas DR. 2006. Potassium glutamate as a transcriptional inhibitor during bacterial osmoregulation. EMBO J 25:1515–21
     [Google Scholar]
  50. 50. 
    Guo F, Adhya S 2007. Spiral structure of Escherichia coli HUαβ provides foundation for DNA supercoiling. PNAS 104:4309–14
     [Google Scholar]
  51. 51. 
    Guo MS, Haakonsen DL, Zeng W, Schumacher MA, Laub MT. 2018. A bacterial chromosome structuring protein binds overtwisted DNA to stimulate type II topoisomerases and enable DNA replication. Cell 175:583–97.e23
     [Google Scholar]
  52. 52. 
    Guo X, Myasnikov AG, Chen J, Crucifix C, Papai G et al. 2018. Structural basis for NusA stabilized transcriptional pausing. Mol. Cell 69:816–27.e4
     [Google Scholar]
  53. 53. 
    Ha KS, Toulokhonov I, Vassylyev DG, Landick R. 2010. The NusA N-terminal domain is necessary and sufficient for enhancement of transcriptional pausing via interaction with the RNA exit channel of RNA polymerase. J. Mol. Biol. 401:708–25
     [Google Scholar]
  54. 54. 
    Harden TT, Herlambang KS, Chamberlain M, Lalanne J-B, Wells CD et al. 2020. Alternative transcription cycle for bacterial RNA polymerase. Nat. Commun. 11:448
     [Google Scholar]
  55. 55. 
    Harden TT, Wells CD, Friedman LJ, Landick R, Hochschild A et al. 2016. Bacterial RNA polymerase can retain σ70 throughout transcription. PNAS 113:602–7
     [Google Scholar]
  56. 56. 
    Hatoum A, Roberts J. 2008. Prevalence of RNA polymerase stalling at Escherichia coli promoters after open complex formation. Mol. Microbiol. 68:17–28
     [Google Scholar]
  57. 57. 
    Hein PP, Kolb KE, Windgassen T, Bellecourt MJ, Darst SA et al. 2014. RNA polymerase pausing and nascent-RNA structure formation are linked through clamp-domain movement. Nat. Struct. Mol. Biol. 21:794–802
     [Google Scholar]
  58. 58. 
    Henry KK, Ross W, Myers KS, Lemmer KC, Vera JM et al. 2020. A majority of Rhodobacter sphaeroides promoters lack a crucial RNA polymerase recognition feature, enabling coordinated transcription activation. PNAS 117:29658–68
     [Google Scholar]
  59. 59. 
    Herbert KM, Zhou J, Mooney RA, Porta AL, Landick R, Block SM. 2010. E. coli NusG inhibits backtracking and accelerates pause-free transcription by promoting forward translocation of RNA polymerase. J. Mol. Biol. 399:17–30
     [Google Scholar]
  60. 60. 
    Herbert R, La Porta A, Wong B, Mooney R, Neuman K et al. 2006. Sequence-resolved detection of pausing by single RNA polymerase molecules. Cell 125:1083–94
     [Google Scholar]
  61. 61. 
    Hollands K, Sevostiyanova A, Groisman EA 2014. Unusually long-lived pause required for regulation of a Rho-dependent transcription terminator. PNAS 111:E1999–2007
     [Google Scholar]
  62. 62. 
    Huang YH, Hilal T, Loll B, Burger J, Mielke T et al. 2020. Structure-based mechanisms of a molecular RNA polymerase/chaperone machine required for ribosome biosynthesis. Mol. Cell 79:1024–36.e5
     [Google Scholar]
  63. 63. 
    Imashimizu M, Kireeva ML, Lubkowska L, Gotte D, Parks AR et al. 2013. Intrinsic translocation barrier as an initial step in pausing by RNA polymerase II. J. Mol. Biol. 425:697–712
     [Google Scholar]
  64. 64. 
    Imashimizu M, Takahashi H, Oshima T, McIntosh C, Bubunenko M et al. 2015. Visualizing translocation dynamics and nascent transcript errors in paused RNA polymerases in vivo. Genome Biol 16:98
     [Google Scholar]
  65. 65. 
    Janissen R, Arens MMA, Vtyurina NN, Rivai Z, Sunday ND et al. 2018. Global DNA compaction in stationary-phase bacteria does not affect transcription. Cell 174:1188–99.e14
     [Google Scholar]
  66. 66. 
    Johnson GE, Lalanne JB, Peters ML, Li GW. 2020. Functionally uncoupled transcription-translation in Bacillus subtilis. Nature 585:124–28
     [Google Scholar]
  67. 67. 
    Kamarthapu V, Epshtein V, Benjamin B, Proshkin S, Mironov A et al. 2016. ppGpp couples transcription to DNA repair in E. coli. Science 352:993–96
     [Google Scholar]
  68. 68. 
    Kang JY, Mishanina TV, Bellecourt MJ, Mooney RA, Darst SA, Landick R. 2018. RNA polymerase accommodates a pause RNA hairpin by global conformational rearrangements that prolong pausing. Mol. Cell 69:802–15.e5
     [Google Scholar]
  69. 69. 
    Kang JY, Mishanina TV, Landick R, Darst SA. 2019. Mechanisms of transcriptional pausing in bacteria. J. Mol. Biol. 431:4007–29
     [Google Scholar]
  70. 70. 
    Kang JY, Mooney RA, Nedialkov Y, Saba J, Mishanina TV et al. 2018. Structural basis for transcript elongation control by NusG/RfaH universal regulators. Cell 173:1650–62.e14
     [Google Scholar]
  71. 71. 
    Kang JY, Olinares PD, Chen J, Campbell EA, Mustaev A et al. 2017. Structural basis of transcription arrest by coliphage HK022 Nun in an Escherichia coli RNA polymerase elongation complex. eLife 6:e25478
     [Google Scholar]
  72. 72. 
    Kapanidis AN, Margeat E, Laurence TA, Doose S, Ho SO et al. 2005. Retention of transcription initiation factor σ70 in transcription elongation: single-molecule analysis. Mol. Cell 20:347–56
     [Google Scholar]
  73. 73. 
    Kassavetis GA, Chamberlin MJ. 1981. Pausing and termination of transcription within the early region of bacteriophage T7 DNA in vitro. J. Biol. Chem. 256:2777–86
     [Google Scholar]
  74. 74. 
    Kim S, Beltran B, Irnov I, Jacobs-Wagner C. 2019. Long-distance cooperative and antagonistic RNA polymerase dynamics via DNA supercoiling. Cell 179:106–19.e16
     [Google Scholar]
  75. 75. 
    Kingston RE, Chamberlin MJ. 1981. Pausing and attenuation of in vitro transcription in the rrnB operon of E. coli. Cell 27:523–31
     [Google Scholar]
  76. 76. 
    Kireeva ML, Kashlev M 2009. Mechanism of sequence-specific pausing of bacterial RNA polymerase. PNAS 106:8900–5
     [Google Scholar]
  77. 77. 
    Kohler R, Mooney RA, Mills DJ, Landick R, Cramer P. 2017. Architecture of a transcribing-translating expressome. Science 356:194–97
     [Google Scholar]
  78. 78. 
    Kontur WS, Saecker RM, Davis CA, Capp MW, Record MT Jr. 2006. Solute probes of conformational changes in open complex (RPo) formation by Escherichia coli RNA polymerase at the λPR promoter: evidence for unmasking of the active site in the isomerization step and for large-scale coupled folding in the subsequent conversion to RPo. Biochemistry 45:2161–77
     [Google Scholar]
  79. 79. 
    Kornberg A. 1991. Understanding life as chemistry. Clin. Chem. 37:1895–99
     [Google Scholar]
  80. 80. 
    Kotlajich MV, Hron DR, Boudreau BA, Sun Z, Lyubchenko YL, Landick R 2015. Bridged filaments of histone-like nucleoid structuring protein pause RNA polymerase and aid termination in bacteria. eLife 4:e04970
     [Google Scholar]
  81. 81. 
    Krohn M, Pardon B, Wagner R. 1992. Effects of template topology on RNA polymerase pausing during in vitro transcription of the Escherichia coli rrnB leader region. Mol. Microbiol. 6:581–89
     [Google Scholar]
  82. 82. 
    Krohn M, Wagner R. 1996. Transcriptional pausing of RNA polymerase in the presence of guanosine tetraphosphate depends on the promoter and gene sequence. J. Biol. Chem. 271:23884–94
     [Google Scholar]
  83. 83. 
    Kusuya Y, Kurokawa K, Ishikawa S, Ogasawara N, Oshima T. 2011. Transcription factor GreA contributes to resolving promoter-proximal pausing of RNA polymerase in Bacillus subtilis cells. J. Bacteriol. 193:3090–99
     [Google Scholar]
  84. 84. 
    Kuzminov A. 2018. When DNA topology turns deadly—RNA polymerases dig in their R-loops to stand their ground: new positive and negative (super)twists in the replication-transcription conflict. Trends Genet 34:111–20
     [Google Scholar]
  85. 85. 
    LaFlamme SE, Kramer FR, Mills DR. 1985. Comparison of pausing during transcription and replication. Nucleic Acids Res 13:8425–40
     [Google Scholar]
  86. 86. 
    Lal A, Dhar A, Trostel A, Kouzine F, Seshasayee AS, Adhya S. 2016. Genome scale patterns of supercoiling in a bacterial chromosome. Nat. Commun. 7:11055
     [Google Scholar]
  87. 87. 
    Landick R. 2006. The regulatory roles and mechanism of transcriptional pausing. Biochem. Soc. Transact. 34:1062–66
     [Google Scholar]
  88. 88. 
    Landick R, Carey J, Yanofsky C 1985. Translation activates the paused transcription complex and restores transcription of the trp operon leader region. PNAS 82:4663–67
     [Google Scholar]
  89. 89. 
    Landick R, Wang D, Chan C 1996. Quantitative analysis of transcriptional pausing by RNA polymerase: the his leader pause site as a paradigm. Methods Enzymol 274:334–52
     [Google Scholar]
  90. 90. 
    Larson MH, Mooney RA, Peters JM, Windgassen T, Nayak D et al. 2014. A pause sequence enriched at translation start sites drives transcription dynamics in vivo. Science 344:1042–47
     [Google Scholar]
  91. 91. 
    Lee SJ, Gralla JD. 2004. Osmo-regulation of bacterial transcription via poised RNA polymerase. Mol. Cell 14:153–62
     [Google Scholar]
  92. 92. 
    Liu B, Zuo Y, Steitz TA 2016. Structures of E. coli σS-transcription initiation complexes provide new insights into polymerase mechanism. PNAS 113:4051–56
     [Google Scholar]
  93. 93. 
    Liu LF, Wang JC 1987. Supercoiling of the DNA template during transcription. PNAS 84:7024–27
     [Google Scholar]
  94. 94. 
    Lyakhov DL, He B, Zhang X, Studier FW, Dunn JJ, McAllister WT. 1998. Pausing and termination by bacteriophage T7 RNA polymerase. J. Mol. Biol. 280:201–13
     [Google Scholar]
  95. 95. 
    Ma J, Bai L, Wang MD. 2013. Transcription under torsion. Science 340:1580–83
     [Google Scholar]
  96. 96. 
    Ma J, Tan C, Gao X, Fulbright RM Jr., Roberts JW, Wang MD 2019. Transcription factor regulation of RNA polymerase's torque generation capacity. PNAS 116:2583–88
     [Google Scholar]
  97. 97. 
    Maizels NM. 1973. The nucleotide sequence of the lactose messenger ribonucleic acid transcribed from the UV5 promoter mutant of Escherichia coli. PNAS 70:3585–89
     [Google Scholar]
  98. 98. 
    Malone B, Chen J, Wang Q, Llewellyn E, Choi YJ et al. 2021. Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. PNAS 118:e2102516118
     [Google Scholar]
  99. 99. 
    Mandell ZF, Oshiro RT, Yakhnin AV, Vishwakarma R, Kashlev M et al. 2021. NusG is an intrinsic transcription termination factor that stimulates motility and coordinates gene expression with NusA. eLife 10:e61880
     [Google Scholar]
  100. 100. 
    Marr MT, Roberts JW. 2000. Function of transcription cleavage factors GreA and GreB at a regulatory pause site. Mol. Cell 6:1275–85
     [Google Scholar]
  101. 101. 
    Mayer A, Landry HM, Churchman LS. 2017. Pause & go: from the discovery of RNA polymerase pausing to its functional implications. Curr. Opin. Cell Biol. 46:72–80
     [Google Scholar]
  102. 102. 
    Mondal S, Yakhnin AV, Sebastian A, Albert I, Babitzke P 2016. NusA-dependent transcription termination prevents misregulation of global gene expression. Nat. Microbiol. 1:15007
     [Google Scholar]
  103. 103. 
    Mooney R, Artsimovitch I, Landick R. 1998. Information processing by RNA polymerase: recognition of regulatory signals during RNA chain elongation. J. Bacteriol. 180:3265–75
     [Google Scholar]
  104. 104. 
    Mooney RA, Davis SE, Peters JM, Rowland JL, Ansari AZ, Landick R. 2009. Regulator trafficking on bacterial transcription units in vivo. Mol. Cell 33:97–108
     [Google Scholar]
  105. 105. 
    Mooney RA, Landick R. 2003. Tethering σ70 to RNA polymerase reveals high in vivo activity of σ factors and σ70-dependent pausing at promoter-distal locations. Genes Dev 17:2839–51
     [Google Scholar]
  106. 106. 
    Mosrin-Huaman C, Turnbough CL Jr., Rahmouni AR. 2004. Translocation of Escherichia coli RNA polymerase against a protein roadblock in vivo highlights a passive sliding mechanism for transcript elongation. Mol. Microbiol. 51:1471–81
     [Google Scholar]
  107. 107. 
    Mustaev A, Roberts J, Gottesman M. 2017. Transcription elongation. Transcription 8:150–61
     [Google Scholar]
  108. 108. 
    Nechooshtan G, Elgrably-Weiss M, Altuvia S 2014. Changes in transcriptional pausing modify the folding dynamics of the pH-responsive RNA element. Nucleic Acids Res 42:622–30
     [Google Scholar]
  109. 109. 
    Nedialkov Y, Svetlov D, Belogurov GA, Artsimovitch I. 2018. Locking the non-template DNA to control transcription. Mol. Microbiol. 109:445–57
     [Google Scholar]
  110. 110. 
    Neuman K, Abbondanzieri E, Landick R, Gelles J, Block SM. 2003. Ubiquitous transcriptional pausing is independent of RNA polymerase backtracking. Cell 115:437–47
     [Google Scholar]
  111. 111. 
    Nickels BE, Mukhopadhyay J, Garrity SJ, Ebright RH, Hochschild A. 2004. The σ70 subunit of RNA polymerase mediates a promoter-proximal pause at the lac promoter. Nat. Struct. Mol. Biol. 11:544–50
     [Google Scholar]
  112. 112. 
    Nudler E. 2012. RNA polymerase backtracking in gene regulation and genome instability. Cell 149:1438–45
     [Google Scholar]
  113. 113. 
    Nudler E, Mustaev A, Lukhtanov E, Goldfarb A. 1997. The RNA:DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase. Cell 89:33–41
     [Google Scholar]
  114. 114. 
    O'Reilly FJ, Xue L, Graziadei A, Sinn L, Lenz S et al. 2020. In-cell architecture of an actively transcribing-translating expressome. Science 369:554–57
     [Google Scholar]
  115. 115. 
    Paitan Y, Orr E, Ron EZ, Rosenberg E 1999. A NusG-like transcription anti-terminator is involved in the biosynthesis of the polyketide antibiotic TA of Myxococcus xanthus. FEMS Microbiol. Lett. 170:221–27
     [Google Scholar]
  116. 116. 
    Perdue S, Roberts J. 2010. A backtrack-inducing sequence is an essential component of Escherichia coli σ70-dependent promoter-proximal pausing. Mol. Microbiol. 78:636–50
     [Google Scholar]
  117. 117. 
    Perdue SA, Roberts JW. 2011. σ70-dependent transcription pausing in Escherichia coli. J. Mol. Biol. 412:782–92
     [Google Scholar]
  118. 118. 
    Peters JM, Mooney RA, Grass JA, Jessen ED, Tran F, Landick R. 2012. Rho and NusG suppress pervasive antisense transcription in Escherichia coli. Genes Dev 26:2621–33
     [Google Scholar]
  119. 119. 
    Petushkov I, Esyunina D, Kulbachinskiy A. 2017. Possible roles of sigma-dependent RNA polymerase pausing in transcription regulation. RNA Biol 14:1678–82
     [Google Scholar]
  120. 120. 
    Prieto AI, Kahramanoglou C, Ali RM, Fraser GM, Seshasayee AS, Luscombe NM. 2012. Genomic analysis of DNA binding and gene regulation by homologous nucleoid-associated proteins IHF and HU in Escherichia coli K12. Nucleic Acids Res 40:3524–37
     [Google Scholar]
  121. 121. 
    Proshkin S, Rahmouni AR, Mironov A, Nudler E. 2010. Cooperation between translating ribosomes and RNA polymerase in transcription elongation. Science 328:504–8
     [Google Scholar]
  122. 122. 
    Record MT Jr., Courtenay ES, Cayley DS, Guttman HJ. 1998. Responses of E. coli to osmotic stress: large changes in amounts of cytoplasmic solutes and water. Trends Biochem. Sci. 23:143–48
     [Google Scholar]
  123. 123. 
    Revyakin A, Liu C, Ebright RH, Strick TR. 2006. Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching. Science 314:1139–43
     [Google Scholar]
  124. 124. 
    Ring B, Yarnell W, Roberts J. 1996. Function of E. coli RNA polymerase σ factor σ70 in promoter-proximal pausing. Cell 86:485–93
     [Google Scholar]
  125. 125. 
    Ring BZ, Roberts JW. 1994. Function of a nontranscribed DNA strand site in transcription elongation. Cell 78:317–24
     [Google Scholar]
  126. 126. 
    Ross W, Sanchez-Vazquez P, Chen AY, Lee JH, Burgos HL, Gourse RL. 2016. ppGpp binding to a site at the RNAP-DksA interface accounts for its dramatic effects on transcription initiation during the stringent response. Mol. Cell 62:811–23
     [Google Scholar]
  127. 127. 
    Saba J, Chua XY, Mishanina TV, Nayak D, Windgassen TA et al. 2019. The elemental mechanism of transcriptional pausing. eLife 8:e40981
     [Google Scholar]
  128. 128. 
    Sekine S, Murayama Y, Svetlov V, Nudler E, Yokoyama S. 2015. The ratcheted and ratchetable structural states of RNA polymerase underlie multiple transcriptional functions. Mol. Cell 57:408–21
     [Google Scholar]
  129. 129. 
    Shen BA, Landick R. 2019. Transcription of bacterial chromatin. J. Mol. Biol. 431:4040–66
     [Google Scholar]
  130. 130. 
    Shikalov AB, Esyunina DM, Pupov DV, Kulbachinskiy AV, Petushkov IV. 2019. The σ24 subunit of Escherichia coli RNA polymerase can induce transcriptional pausing in vitro. Biochemistry 84:426–34
     [Google Scholar]
  131. 131. 
    Silva DA, Weiss DR, Pardo Avila F, Da LT, Levitt M et al. 2014. Millisecond dynamics of RNA polymerase II translocation at atomic resolution. PNAS 111:7665–70
     [Google Scholar]
  132. 132. 
    Sivaramakrishnan P, Gordon AJE, Halliday JA, Herman C. 2018. How acts of infidelity promote DNA break repair: collision and collusion between DNA repair and transcription. BioEssays 40:e1800045
     [Google Scholar]
  133. 133. 
    Sorensen MA, Jensen KF, Pedersen S. 1994. High concentrations of ppGpp decrease the RNA chain growth rate: implications for protein synthesis and translational fidelity during amino acid starvation in Escherichia coli. J. Mol. Biol. 236:441–54
     [Google Scholar]
  134. 134. 
    Strobel EJ, Roberts JW. 2014. Regulation of promoter-proximal transcription elongation: Enhanced DNA scrunching drives λQ antiterminator-dependent escape from a σ70-dependent pause. Nucleic Acids Res 42:5097–108
     [Google Scholar]
  135. 135. 
    Strobel EJ, Roberts JW. 2015. Two transcription pause elements underlie a σ70-dependent pause cycle. PNAS 112:e4374–80
     [Google Scholar]
  136. 136. 
    Thomas MJ, Platas AA, Hawley DK. 1998. Transcriptional fidelity and proofreading by RNA polymerase II. Cell 93:627–37
     [Google Scholar]
  137. 137. 
    Toulokhonov I, Artsimovitch I, Landick R. 2001. Allosteric control of RNA polymerase by a site that contacts nascent RNA hairpins. Science 292:730–33
     [Google Scholar]
  138. 138. 
    Turnbough CL Jr. 2019. Regulation of bacterial gene expression by transcription attenuation. Microbiol. Mol. Biol. Rev. 83:e00019-19
     [Google Scholar]
  139. 139. 
    Turnbough CL Jr., Hicks KL, Donahue JP 1983. Attenuation control of pyrBI operon expression in Escherichia coli K-12. PNAS 80:368–72
     [Google Scholar]
  140. 140. 
    Turtola M, Belogurov GA 2016. NusG inhibits RNA polymerase backtracking by stabilizing the minimal transcription bubble. eLife 5:e18096
     [Google Scholar]
  141. 141. 
    Van Wynsberghe A, Li G, Cui Q 2004. Normal-mode analysis suggests protein flexibility modulation throughout RNA polymerase's functional cycle. Biochemistry 43:13083–96
     [Google Scholar]
  142. 142. 
    Vera JM, Ghosh IN, Zhang Y, Hebert AS, Coon JJ, Landick R. 2020. Genome-scale transcription-translation mapping reveals features of Zymomonas mobilis transcription units and promoters. mSystems 5:e00250-20
     [Google Scholar]
  143. 143. 
    Vos SM, Farnung L, Urlaub H, Cramer P. 2018. Structure of paused transcription complex Pol II-DSIF-NELF. Nature 560:601–6
     [Google Scholar]
  144. 144. 
    Vvedenskaya IO, Vahedian-Movahed H, Bird JG, Knoblauch JG, Goldman SR et al. 2014. Interactions between RNA polymerase and the “core recognition element” counteract pausing. Science 344:1285–89
     [Google Scholar]
  145. 145. 
    Wang C, Molodtsov V, Firlar E, Kaelber JT, Blaha G et al. 2020. Structural basis of transcription-translation coupling. Science 369:1359–65
     [Google Scholar]
  146. 146. 
    Webster MW, Takacs M, Zhu C, Vidmar V, Eduljee A et al. 2020. Structural basis of transcription-translation coupling and collision in bacteria. Science 369:1355–59
     [Google Scholar]
  147. 147. 
    Weixlbaumer A, Leon K, Landick R, Darst SA. 2013. Structural basis of transcriptional pausing in bacteria. Cell 152:431–41
     [Google Scholar]
  148. 148. 
    Wickiser JK, Winkler WC, Breaker RR, Crothers DM. 2005. The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Mol. Cell 18:49–60
     [Google Scholar]
  149. 149. 
    Widom JR, Nedialkov YA, Rai V, Hayes RL, Brooks CL 3rd et al. 2018. Ligand modulates cross-coupling between riboswitch folding and transcriptional pausing. Mol. Cell 72:541–52.e6
     [Google Scholar]
  150. 150. 
    Windgassen T, Mooney RA, Nayak D, Palangat M, Zhang J, Landick R. 2014. Trigger-helix folding pathway and SI3 mediate catalysis and hairpin-stabilized pausing by Escherichia coli RNA polymerase. Nucleic Acids Res 42:12707–21
     [Google Scholar]
  151. 151. 
    Winkler ME, Yanofsky C. 1981. Pausing of RNA polymerase during in vitro transcription of the tryptophan operon leader region. Biochemistry 20:3738–44
     [Google Scholar]
  152. 152. 
    Yakhnin AV, Babitzke P 2002. NusA-stimulated RNA polymerase pausing and termination participates in the Bacillus subtilis trp operon attenuation mechanism in vitro. PNAS 99:11067–72
     [Google Scholar]
  153. 153. 
    Yakhnin AV, FitzGerald PC, McIntosh C, Yakhnin H, Kireeva M et al. 2020. NusG controls transcription pausing and RNA polymerase translocation throughout the Bacillus subtilis genome. PNAS 117:21628–36
     [Google Scholar]
  154. 154. 
    Yakhnin AV, Kashlev M, Babitzke P. 2020. NusG-dependent RNA polymerase pausing is a frequent function of this universally conserved transcription elongation factor. Crit. Rev. Biochem. Mol. Biol. 55:716–28
     [Google Scholar]
  155. 155. 
    Yakhnin AV, Murakami KS, Babitzke P. 2016. NusG is a sequence-specific RNA polymerase pause factor that binds to the non-template DNA within the paused transcription bubble. J. Biol. Chem. 291:5299–308
     [Google Scholar]
  156. 156. 
    Zamft B, Bintu L, Ishibashi T, Bustamante C 2012. Nascent RNA structure modulates the transcriptional dynamics of RNA polymerases. PNAS 109:8948–53
     [Google Scholar]
  157. 157. 
    Zhang J, Landick R. 2016. A two-way street: regulatory interplay between RNA polymerase and nascent RNA structure. Trends Biochem. Sci. 41:293–310
     [Google Scholar]
  158. 158. 
    Zhang L, Pardo-Avila F, Unarta IC, Cheung PP, Wang G et al. 2016. Elucidation of the dynamics of transcription elongation by RNA polymerase II using kinetic network models. Acc. Chem. Res. 49:687–94
     [Google Scholar]
  159. 159. 
    Zhou J, Ha KS, La Porta A, Landick R, Block SM 2011. Applied force provides insight into transcriptional pausing and its modulation by transcription factor NusA. Mol. Cell 44:635–46
     [Google Scholar]
  160. 160. 
    Zhu M, Mori M, Hwa T, Dai X 2019. Disruption of transcription-translation coordination in Escherichia coli leads to premature transcriptional termination. Nat. Microbiol. 4:2347–56
     [Google Scholar]
/content/journals/10.1146/annurev-micro-051721-043826
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Transcriptional Pausing as a Mediator of Bacterial Gene Regulation
Annual Review of Microbiology 75, 291 (2021); https://doi.org/10.1146/annurev-micro-051721-043826
/content/journals/10.1146/annurev-micro-051721-043826
/content/journals/10.1146/annurev-micro-051721-043826
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