Transcription elongation: Heterogeneous tracking of RNA polymerase and its biological implications

Transcription

Volumn 5, Issue FEB, 2014, Pages

  Iimashimizu, Masahiko ^a   Shimamoto, Nobuo ^b   Oshima, Taku ^c   Kashlev, Mikhail ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b KYOTO SANGYO UNIVERSITY   (Japan)

^c NARA INSTITUTE OF SCIENCE AND TECHNOLOGY   (Japan)

Author keywords

Brownian ratchet; Power stroke; RNA polymerase; Sequence heterogeneity of DNA; Transcription elongation factors; Transcription pausing; Translocation

Indexed keywords

RNA POLYMERASE; DNA; DNA DIRECTED RNA POLYMERASE; RNA;

ARTICLE; CRYSTAL STRUCTURE; DNA SEQUENCE; DOWNSTREAM PROCESSING; ESCHERICHIA COLI; GENE TRANSLOCATION; GENETIC HETEROGENEITY; HUMAN; SEQUENCE ANALYSIS; TRANSCRIPTION ELONGATION; BACTERIUM; BIOLOGICAL MODEL; BIOSYNTHESIS; CHEMICAL STRUCTURE; CHEMISTRY; EUKARYOTE; GENETICS; METABOLISM; NUCLEOTIDE SEQUENCE; PHYSIOLOGY;

BACTERIA; BASE SEQUENCE; DNA; DNA-DIRECTED RNA POLYMERASES; EUKARYOTA; MODELS, GENETIC; MODELS, MOLECULAR; RNA; TRANSCRIPTION ELONGATION, GENETIC;

EID: 84901677567     PISSN: 21541264     EISSN: 21541272     Source Type: Journal    
DOI: 10.4161/trns.28285     Document Type: Article

References (105)

1. Komissarova N, Becker J, Solter S, Kireeva M, Kashlev M. Shortening of RNA:DNA hybrid in the elongation complex of RNA polymerase is a prerequisite for transcription termination. Mol Cell 2002; 10:1151-62; PMID:12453422; http://dx.doi.org/10.1016/S1097-2765(02)00738-4
2. Adelman K, Lis JT. Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat Rev Genet 2012; 13:720-31; PMID:22986266; http://dx.doi.org/10.1038/nrg3293
3. Landick R. The regulatory roles and mechanism of transcriptional pausing. Biochem Soc Trans 2006; 34:1062-6; PMID:17073751; http://dx.doi.org/10.1042/BST0341062
4. Landick R, Carey J, Yanofsky C. Translation activates the paused transcription complex and restores transcription of the trp operon leader region. Proc Natl Acad Sci U S A 1985; 82:4663-7; PMID:2991886; http://dx.doi.org/10.1073/pnas.82.14.4663
5. Artsimovitch I, Landick R. The transcriptional regulator RfaH stimulates RNA chain synthesis after recruitment to elongation complexes by the exposed nontemplate DNA strand. Cell 2002; 109:193-203; PMID:12007406; http://dx.doi.org/10.1016/S0092-8674(02)00724-9
6. Roberts JW, Yarnell W, Bartlett E, Guo J, Marr M, Ko DC, Sun H, Roberts CW. Antitermination by bacteriophage lambda Q protein. Cold Spring Harb Symp Quant Biol 1998; 63:319-25; PMID:10384296; http://dx.doi.org/10.1101/sqb.1998.63.319
7. Shukla S, Kavak E, Gregory M, Imashimizu M, Shutinoski B, Kashlev M, Oberdoerffer P, Sandberg R, Oberdoerffer S. CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 2011; 479:74-9; PMID:21964334; http://dx.doi.org/10.1038/nature10442
8. Nudler E, Mustaev A, Lukhtanov E, Goldfarb A. The RNA-DNA hybrid maintains the register of transcription by preventing backtracking of RNA polymerase. Cell 1997; 89:33-41; PMID:9094712; http://dx.doi.org/10.1016/S0092-8674(00)80180-4
9. Komissarova N, Kashlev M. RNA polymerase switches between inactivated and activated states By translocating back and forth along the DNA and the RNA. J Biol Chem 1997; 272:15329-38; PMID:9182561; http://dx.doi.org/10.1074/jbc.272.24.15329
10. Churchman LS, Weissman JS. Nascent transcript sequencing visualizes transcription at nucleotide resolution. Nature 2011; 469:368-73; PMID:21248844; http://dx.doi.org/10.1038/nature09652
11. Perdue SA, Roberts JW. A backtrack-inducing sequence is an essential component of Escherichia coli σ(70)-dependent promoter-proximal pausing. Mol Microbiol 2010; 78:636-50; PMID:21382107; http://dx.doi.org/10.1111/j.1365-2958.2010.07347.x
12. Muse GW, Gilchrist DA, Nechaev S, Shah R, Parker JS, Grissom SF, Zeitlinger J, Adelman K. RNA polymerase is poised for activation across the genome. Nat Genet 2007; 39:1507-11; PMID:17994021; http://dx.doi.org/10.1038/ng.2007.21
13. Nechaev S, Fargo DC, dos Santos G, Liu L, Gao Y, Adelman K. Global analysis of short RNAs reveals widespread promoter-proximal stalling and arrest of Pol II in Drosophila. Science 2010; 327:335-8; PMID:20007866; http://dx.doi.org/10.1126/science.1181421
14. Imashimizu M, Oshima T, Lubkowska L, Kashlev M. Direct assessment of transcription fidelity by high-resolution RNA sequencing. Nucleic Acids Res 2013; 41:9090-104; PMID:23925128; http://dx.doi.org/10.1093/nar/gkt698
15. Dutta D, Shatalin K, Epshtein V, Gottesman ME, Nudler E. Linking RNA polymerase backtracking to genome instability in E. coli. Cell 2011; 146:533-43; PMID:21854980; http://dx.doi.org/10.1016/j.cell.2011.07.034
16. Nudler E. RNA polymerase backtracking in gene regulation and genome instability. Cell 2012; 149:1438-45; PMID:22726433; http://dx.doi.org/10.1016/j.cell.2012.06.003
17. Aguilera A, García-Muse T. R loops: from transcription byproducts to threats to genome stability. Mol Cell 2012; 46:115-24; PMID:22541554; http://dx.doi.org/10.1016/j.molcel.2012.04.009
18. Helmrich A, Ballarino M, Nudler E, Tora L. Transcription-replication encounters, consequences and genomic instability. Nat Struct Mol Biol 2013; 20:412-8; PMID:23552296; http://dx.doi.org/10.1038/nsmb.2543
19. Borukhov S, Sagitov V, Goldfarb A. Transcript cleavage factors from E. coli. Cell 1993; 72:459-66; PMID:8431948; http://dx.doi.org/10.1016/0092-8674(93)90121-6
20. Izban MG, Luse DS. The RNA polymerase II ternary complex cleaves the nascent transcript in a 3′----5′ direction in the presence of elongation factor SII. Genes Dev 1992; 6:1342-56; PMID:1378419; http://dx.doi.org/10.1101/gad.6.7.1342
21. Reines D, Ghanouni P, Li QQ, Mote J Jr. The RNA polymerase II elongation complex. Factor-dependent transcription elongation involves nascent RNA cleavage. J Biol Chem 1992; 267:15516-22; PMID:1379232
22. Hausner W, Lange U, Musfeldt M. Transcription factor S, a cleavage induction factor of the archaeal RNA polymerase. J Biol Chem 2000; 275:12393-9; PMID:10777522; http://dx.doi.org/10.1074/jbc.275.17.12393
23. Burova E, Hung SC, Sagitov V, Stitt BL, Gottesman ME. Escherichia coli NusG protein stimulates transcription elongation rates in vivo and in vitro. J Bacteriol 1995; 177:1388-92; PMID:7868616
24. Herbert KM, Zhou J, Mooney RA, Porta AL, Landick R, Block SME. E. coli NusG inhibits backtracking and accelerates pause-free transcription by promoting forward translocation of RNA polymerase. J Mol Biol 2010; 399:17-30; PMID:20381500; http://dx.doi.org/10.1016/j.jmb.2010.03.051
25. Torres M, Balada JM, Zellars M, Squires C, Squires CL. In vivo effect of NusB and NusG on rRNA transcription antitermination. J Bacteriol 2004; 186:1304-10; PMID:14973028; http://dx.doi.org/10.1128/JB.186.5.1304-1310.2004
26. Chen H, Contreras X, Yamaguchi Y, Handa H, Peterlin BM, Guo S. Repression of RNA polymerase II elongation in vivo is critically dependent on the C-terminus of Spt5. PLoS One 2009; 4:e6918; PMID:19742326; http://dx.doi.org/10.1371/journal.pone.0006918
27. Hirtreiter A, Damsma GE, Cheung AC, Klose D, Grohmann D, Vojnic E, Martin AC, Cramer P, Werner F. Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif. Nucleic Acids Res 2010; 38:4040-51; PMID:20197319; http://dx.doi.org/10.1093/nar/gkq135
28. Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, Sugimoto S, Yano K, Hartzog GA, Winston F, et al. DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev 1998; 12:343-56; PMID:9450929; http://dx.doi.org/10.1101/gad.12.3.343
29. Shimamoto N. Nanobiology of RNA polymerase: biological consequence of inhomogeneity in reactant. Chem Rev 2013; 113:8400-22; PMID:24074222; http://dx.doi.org/10.1021/cr400006b
30. Oosawa F, Hayashi S. The loose coupling mechanism in molecular machines of living cells. Adv Biophys 1986; 22:151-83; PMID:2882655; http://dx.doi.org/10.1016/0065-227X(86)90005-5
31. Tyska MJ, Warshaw DM. The myosin power stroke. Cell Motil Cytoskeleton 2002; 51:1-15; PMID:11810692; http://dx.doi.org/10.1002/cm.10014
32. Astumian RD. Thermodynamics and kinetics of a Brownian motor. Science 1997; 276:917-22; PMID:9139648; http://dx.doi.org/10.1126/science.276.5314.917
33. Block SM. Kinesin motor mechanics: binding, stepping, tracking, gating, and limping. Biophys J 2007; 92:2986-95; PMID:17325011; http://dx.doi.org/10.1529/biophysj.106.100677
34. Ishii Y, Nishiyama M, Yanagida T. Mechano-chemical coupling of molecular motors revealed by single molecule measurements. Curr Protein Pept Sci 2004; 5:81-7; PMID:15078219; http://dx.doi.org/10.2174/1389203043486838
35. Malinen AM, Turtola M, Parthiban M, Vainonen L, Johnson MS, Belogurov GA. Active site opening and closure control translocation of multisubunit RNA polymerase. Nucleic Acids Res 2012; 40:7442-51; PMID:22570421; http://dx.doi.org/10.1093/nar/gks383
36. Bar-Nahum G, Epshtein V, Ruckenstein AE, Rafikov R, Mustaev A, Nudler E. A ratchet mechanism of transcription elongation and its control. Cell 2005; 120:183-93; PMID:15680325; http://dx.doi.org/10.1016/j.cell.2004.11.045
37. Guajardo R, Sousa R. A model for the mechanism of polymerase translocation. J Mol Biol 1997; 265:8-19; PMID:8995520; http://dx.doi.org/10.1006/jmbi.1996.0707
38. Abbondanzieri EA, Greenleaf WJ, Shaevitz JW, Landick R, Block SM. Direct observation of base-pair stepping by RNA polymerase. Nature 2005; 438:460-5; PMID:16284617; http://dx.doi.org/10.1038/nature04268
39. Imashimizu M, Kireeva ML, Lubkowska L, Gotte D, Parks AR, Strathern JN, Kashlev M. Intrinsic translocation barrier as an initial step in pausing by RNA polymerase II. J Mol Biol 2013; 425:697-712; PMID:23238253; http://dx.doi.org/10.1016/j.jmb.2012.12.002
40. Sigurdsson S, Dirac-Svejstrup AB, Svejstrup JQ. Evidence that transcript cleavage is essential for RNA polymerase II transcription and cell viability. Mol Cell 2010; 38:202-10; PMID:20417599; http://dx.doi.org/10.1016/j.molcel.2010.02.026
41. Hein PP, Palangat M, Landick R. RNA transcript 3′-proximal sequence affects translocation bias of RNA polymerase. Biochemistry 2011; 50:7002-14; PMID:21739957; http://dx.doi.org/10.1021/bi200437q
42. Hawryluk PJ, Ujvári A, Luse DS. Characterization of a novel RNA polymerase II arrest site which lacks a weak 3′ RNA-DNA hybrid. Nucleic Acids Res 2004; 32:1904-16; PMID:15047857; http://dx.doi.org/10.1093/nar/gkh505
43. Herbert KM, La Porta A, Wong BJ, Mooney RA, Neuman KC, Landick R, Block SM. Sequence-resolved detection of pausing by single RNA polymerase molecules. Cell 2006; 125:1083-94; PMID:16777599; http://dx.doi.org/10.1016/j.cell.2006.04.032
44. Nikolova EN, Bascom GD, Andricioaei I, Al-Hashimi HM. Probing sequence-specific DNA flexibility in a-tracts and pyrimidine-purine steps by nuclear magnetic resonance (13)C relaxation and molecular dynamics simulations. Biochemistry 2012; 51:8654-64; PMID:23035755; http://dx.doi.org/10.1021/bi3009517
45. Duchardt E, Nilsson L, Schleucher J. Cytosine ribose flexibility in DNA: a combined NMR 13C spin relaxation and molecular dynamics simulation study. Nucleic Acids Res 2008; 36:4211-9; PMID:18579564; http://dx.doi.org/10.1093/nar/gkn375
46. Artsimovitch I, Landick R. Pausing by bacterial RNA polymerase is mediated by mechanistically distinct classes of signals. Proc Natl Acad Sci U S A 2000; 97:7090-5; PMID:10860976; http://dx.doi.org/10.1073/pnas.97.13.7090
47. Toulokhonov I, Zhang J, Palangat M, Landick R. A central role of the RNA polymerase trigger loop in active-site rearrangement during transcriptional pausing. Mol Cell 2007; 27:406-19; PMID:17679091; http://dx.doi.org/10.1016/j.molcel.2007.06.008
48. Sydow JF, Brueckner F, Cheung AC, Damsma GE, Dengl S, Lehmann E, Vassylyev D, Cramer P. Structural basis of transcription: mismatch-specific fidelity mechanisms and paused RNA polymerase II with frayed RNA. Mol Cell 2009; 34:710-21; PMID:19560423; http://dx.doi.org/10.1016/j.molcel.2009.06.002
49. Vassylyev DG, Vassylyeva MN, Perederina A, Tahirov TH, Artsimovitch I. Structural basis for transcription elongation by bacterial RNA polymerase. Nature 2007; 448:157-62; PMID:17581590; http://dx.doi.org/10.1038/nature05932
50. Kireeva M, Kashlev M, Burton ZF. Translocation by multi-subunit RNA polymerases. Biochim Biophys Acta 2010; 1799:389-401; PMID:20097318; http://dx.doi.org/10.1016/j.bbagrm.2010.01.007
51. Walmacq C, Cheung AC, Kireeva ML, Lubkowska L, Ye C, Gotte D, Strathern JN, Carell T, Cramer P, Kashlev M. Mechanism of translesion transcription by RNA polymerase II and its role in cellular resistance to DNA damage. Mol Cell 2012; 46:18-29; PMID:22405652; http://dx.doi.org/10.1016/j.molcel.2012.02.006
52. Epshtein V, Toulmé F, Rahmouni AR, Borukhov S, Nudler E. Transcription through the roadblocks: the role of RNA polymerase cooperation. EMBO J 2003; 22:4719-27; PMID:12970184; http://dx.doi.org/10.1093/emboj/cdg452
53. Bintu L, Ishibashi T, Dangkulwanich M, Wu YY, Lubkowska L, Kashlev M, Bustamante C. Nucleosomal elements that control the topography of the barrier to transcription. Cell 2012; 151:738-49; PMID:23141536; http://dx.doi.org/10.1016/j.cell.2012.10.009
54. Vassylyev DG, Vassylyeva MN, Zhang J, Palangat M, Artsimovitch I, Landick R. Structural basis for substrate loading in bacterial RNA polymerase. Nature 2007; 448:163-8; PMID:17581591; http://dx.doi.org/10.1038/nature05931
55. Gnatt AL, Cramer P, Fu J, Bushnell DA, Kornberg RD. Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 A resolution. Science 2001; 292:1876-82; PMID:11313499; http://dx.doi.org/10.1126/science.1059495
56. Westover KD, Bushnell DA, Kornberg RD. Structural basis of transcription: separation of RNA from DNA by RNA polymerase II. Science 2004; 303:1014-6; PMID:14963331; http://dx.doi.org/10.1126/science.1090839
57. Brueckner F, Cramer P. Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation. Nat Struct Mol Biol 2008; 15:811-8; PMID:18552824; http://dx.doi.org/10.1038/nsmb.1458
58. Wang D, Bushnell DA, Westover KD, Kaplan CD, Kornberg RD. Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis. Cell 2006; 127:941-54; PMID:17129781; http://dx.doi.org/10.1016/j.cell.2006.11.023
59. Westover KD, Bushnell DA, Kornberg RD. Structural basis of transcription: nucleotide selection by rotation in the RNA polymerase II active center. Cell 2004; 119:481-9; PMID:15537538; http://dx.doi.org/10.1016/j.cell.2004.10.016
60. Wang D, Bushnell DA, Huang X, Westover KD, Levitt M, Kornberg RD. Structural basis of transcription: backtracked RNA polymerase II at 3.4 angstrom resolution. Science 2009; 324:1203-6; PMID:19478184; http://dx.doi.org/10.1126/science.1168729
61. Weixlbaumer A, Leon K, Landick R, Darst SA. Structural basis of transcriptional pausing in bacteria. Cell 2013; 152:431-41; PMID:23374340; http://dx.doi.org/10.1016/j.cell.2012.12.020
62. Cramer P, Bushnell DA, Kornberg RD. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution. Science 2001; 292:1863-76; PMID:11313498; http://dx.doi.org/10.1126/science.1059493
63. Damsma GE, Cramer P. Molecular basis of transcriptional mutagenesis at 8-oxoguanine. J Biol Chem 2009; 284:31658-63; PMID:19758983; http://dx.doi.org/10.1074/jbc.M109.022764
64. Toulmé F, Mosrin-Huaman C, Artsimovitch I, Rahmouni AR. Transcriptional pausing in vivo: a nascent RNA hairpin restricts lateral movements of RNA polymerase in both forward and reverse directions. J Mol Biol 2005; 351:39-51; PMID:15993420; http://dx.doi.org/10.1016/j.jmb.2005.05.052
65. Toulokhonov I, Artsimovitch I, Landick R. Allosteric control of RNA polymerase by a site that contacts nascent RNA hairpins. Science 2001; 292:730-3; PMID:11326100; http://dx.doi.org/10.1126/science.1057738
66. Mosrin-Huaman C, Turnbough CL Jr., Rahmouni AR. Translocation of Escherichia coli RNA polymerase against a protein roadblock in vivo highlights a passive sliding mechanism for transcript elongation. Mol Microbiol 2004; 51:1471-81; PMID:14982639; http://dx.doi.org/10.1111/j.1365-2958.2003.03926.x
67. Saeki H, Svejstrup JQ. Stability, flexibility, and dynamic interactions of colliding RNA polymerase II elongation complexes. Mol Cell 2009; 35:191-205; PMID:19647516; http://dx.doi.org/10.1016/j.molcel.2009.06.009
68. Hung SC, Gottesman ME. The Nun protein of bacteriophage HK022 inhibits translocation of Escherichia coli RNA polymerase without abolishing its catalytic activities. Genes Dev 1997; 11:2670-8; PMID:9334329; http://dx.doi.org/10.1101/gad.11.20.2670
69. Yakhnin AV, Babitzke P. Mechanism of NusG-stimulated pausing, hairpin-dependent pause site selection and intrinsic termination at overlapping pause and termination sites in the Bacillus subtilis trp leader. Mol Microbiol 2010; 76:690-705; PMID:20384694; http://dx.doi.org/10.1111/j.1365-2958.2010.07126.x
70. Yakhnin AV, Yakhnin H, Babitzke P. Function of the Bacillus subtilis transcription elongation factor NusG in hairpin-dependent RNA polymerase pausing in the trp leader. Proc Natl Acad Sci U S A 2008; 105:16131-6; PMID:18852477; http://dx.doi.org/10.1073/pnas.0808842105
71. Yuzenkova Y, Roghanian M, Bochkareva A, Zenkin N. Tagetitoxin inhibits transcription by stabilizing pre-translocated state of the elongation complex. Nucleic Acids Res 2013; 41:9257-65; PMID:23935117; http://dx.doi.org/10.1093/nar/gkt708
72. Tuske S, Sarafianos SG, Wang X, Hudson B, Sineva E, Mukhopadhyay J, Birktoft JJ, Leroy O, Ismail S, Clark AD Jr., et al. Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation. Cell 2005; 122:541-52; PMID:16122422; http://dx.doi.org/10.1016/j.cell.2005.07.017
73. Kashkina E, Anikin M, Tahirov TH, Kochetkov SN, Vassylyev DG, Temiakov D. Elongation complexes of Thermus thermophilus RNA polymerase that possess distinct translocation conformations. Nucleic Acids Res 2006; 34:4036-45; PMID:16914440; http://dx.doi.org/10.1093/nar/gkl559
74. Mishra S, Mohan S, Godavarthi S, Sen R. The interaction surface of a bacterial transcription elongation factor required for complex formation with an antiterminator during transcription antitermination. J Biol Chem 2013; 288:28089-103; PMID:23913688; http://dx.doi.org/10.1074/jbc.M113.472209
75. Gusarov I, Nudler E. Control of intrinsic transcription termination by N and NusA: the basic mechanisms. Cell 2001; 107:437-49; PMID:11719185; http://dx.doi.org/10.1016/S0092-8674(01)00582-7
76. Tomar SK, Artsimovitch I. NusG-Spt5 proteins-Universal tools for transcription modification and communication. Chem Rev 2013; 113:8604-19; PMID:23638618; http://dx.doi.org/10.1021/cr400064k
77. Klein BJ, Bose D, Baker KJ, Yusoff ZM, Zhang X, Murakami KS. RNA polymerase and transcription elongation factor Spt4/5 complex structure. Proc Natl Acad Sci U S A 2011; 108:546-50; PMID:21187417; http://dx.doi.org/10.1073/pnas.1013828108
78. Rees WA, Weitzel SE, Das A, von Hippel PH. Regulation of the elongation-termination decision at intrinsic terminators by antitermination protein N of phage lambda. J Mol Biol 1997; 273:797-813; PMID:9367773; http://dx.doi.org/10.1006/jmbi.1997.1327
79. Kent T, Kashkina E, Anikin M, Temiakov D. Maintenance of RNA-DNA hybrid length in bacterial RNA polymerases. J Biol Chem 2009; 284:13497-504; PMID:19321439; http://dx.doi.org/10.1074/jbc.M901898200
80. Herbert KM, Zhou J, Mooney RA, Porta AL, Landick R, Block SME. E. coli NusG inhibits backtracking and accelerates pause-free transcription by promoting forward translocation of RNA polymerase. J Mol Biol 2010; 399:17-30; PMID:20381500; http://dx.doi.org/10.1016/j.jmb.2010.03.051
81. Sevostyanova A, Artsimovitch I. Functional analysis of Thermus thermophilus transcription factor NusG. Nucleic Acids Res 2010; 38:7432-45; PMID:20639538; http://dx.doi.org/10.1093/nar/gkq623
82. Robledo R, Gottesman ME, Weisberg RA. Lambda nutR mutations convert HK022 Nun protein from a transcription termination factor to a suppressor of termination. J Mol Biol 1990; 212:635-43; PMID:2139472; http://dx.doi.org/10.1016/0022-2836(90)90226-C
83. Henthorn KS, Friedman DI. Identification of functional regions of the Nun transcription termination protein of phage HK022 and the N antitermination protein of phage lambda using hybrid nun-N genes. J Mol Biol 1996; 257:9-20; PMID:8632463; http://dx.doi.org/10.1006/jmbi.1996.0142
84. Zeitlinger J, Stark A, Kellis M, Hong JW, Nechaev S, Adelman K, Levine M, Young RA. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat Genet 2007; 39:1512-6; PMID:17994019; http://dx.doi.org/10.1038/ng.2007.26
85. Kim TH, Barrera LO, Zheng M, Qu C, Singer MA, Richmond TA, Wu Y, Green RD, Ren B. A high-resolution map of active promoters in the human genome. Nature 2005; 436:876-80; PMID:15988478; http://dx.doi.org/10.1038/nature03877
86. Guenther MG, Levine SS, Boyer LA, Jaenisch R, Young RA. A chromatin landmark and transcription initiation at most promoters in human cells. Cell 2007; 130:77-88; PMID:17632057; http://dx.doi.org/10.1016/j.cell.2007.05.042
87. Levine M. Paused RNA polymerase II as a developmental checkpoint. Cell 2011; 145:502-11; PMID:21565610; http://dx.doi.org/10.1016/j.cell.2011.04.021
88. Adelman K, Marr MT, Werner J, Saunders A, Ni Z, Andrulis ED, Lis JT. Efficient release from promoter-proximal stall sites requires transcript cleavage factor TFIIS. Mol Cell 2005; 17:103-12; PMID:15629721; http://dx.doi.org/10.1016/j.molcel.2004.11.028
89. Gilchrist DA, Fromm G, dos Santos G, Pham LN, McDaniel IE, Burkholder A, Fargo DC, Adelman K. Regulating the regulators: the pervasive effects of Pol II pausing on stimulus-responsive gene networks. Genes Dev 2012; 26:933-44; PMID:22549956; http://dx.doi.org/10.1101/gad.187781.112
90. Boettiger AN, Levine M. Synchronous and stochastic patterns of gene activation in the Drosophila embryo. Science 2009; 325:471-3; PMID:19628867; http://dx.doi.org/10.1126/science.1173976
91. Ghosh SK, Missra A, Gilmour DS. Negative elongation factor accelerates the rate at which heat shock genes are shut off by facilitating dissociation of heat shock factor. Mol Cell Biol 2011; 31:4232-43; PMID:21859888; http://dx.doi.org/10.1128/MCB.05930-11
92. Metzker ML. Sequencing technologies-the next generation. Nat Rev Genet 2010; 11:31-46; PMID:19997069; http://dx.doi.org/10.1038/nrg2626
93. Li J, Liu Y, Rhee HS, Ghosh SK, Bai L, Pugh BF, Gilmour DS. Kinetic competition between elongation rate and binding of NELF controls promoter-proximal pausing. Mol Cell 2013; 50:711-22; PMID:23746353; http://dx.doi.org/10.1016/j.molcel.2013.05.016
94. Stepanova E, Wang M, Severinov K, Borukhov S. Early transcriptional arrest at Escherichia coli rplN and ompX promoters. J Biol Chem 2009; 284:35702-13; PMID:19854830; http://dx.doi.org/10.1074/jbc.M109.053983
95. Marr MT, Roberts JW. Function of transcription cleavage factors GreA and GreB at a regulatory pause site. Mol Cell 2000; 6:1275-85; PMID:11163202; http://dx.doi.org/10.1016/S1097-2765(00)00126-X
96. Hatoum A, Roberts J. Prevalence of RNA polymerase stalling at Escherichia coli promoters after open complex formation. Mol Microbiol 2008; 68:17-28; PMID:18333883; http://dx.doi.org/10.1111/j.1365-2958.2008.06138.x
97. Nickels BE, Mukhopadhyay J, Garrity SJ, Ebright RH, Hochschild A. The sigma 70 subunit of RNA polymerase mediates a promoter-proximal pause at the lac promoter. Nat Struct Mol Biol 2004; 11:544-50; PMID:15122345; http://dx.doi.org/10.1038/nsmb757
98. Wade JT, Struhl K. The transition from transcriptional initiation to elongation. Curr Opin Genet Dev 2008; 18:130-6; PMID:18282700; http://dx.doi.org/10.1016/j.gde.2007.12.008
99. Kubori T, Shimamoto N. A branched pathway in the early stage of transcription by Escherichia coli RNA polymerase. J Mol Biol 1996; 256:449-57; PMID:8604130; http://dx.doi.org/10.1006/jmbi.1996.0100
100. Sen R, Nagai H, Hernandez VJ, Shimamoto N. Reduction in abortive transcription from the lambdaPR promoter by mutations in region 3 of the sigma70 subunit of Escherichia coli RNA polymerase. J Biol Chem 1998; 273:9872-7; PMID:9545328; http://dx.doi.org/10.1074/jbc.273.16.9872
101. Susa M, Kubori T, Shimamoto N. A pathway branching in transcription initiation in Escherichia coli. Mol Microbiol 2006; 59:1807-17; PMID:16553885; http://dx.doi.org/10.1111/j.1365-2958.2006.05058.x
102. Imashimizu M, Tanaka K, Shimamoto N. Comparative Study of Cyanobacterial and E. coli RNA Polymerases: Misincorporation, Abortive Transcription, and Dependence on Divalent Cations. Genet Res Int 2011; 2011:572689; PMID:22567357; http://dx.doi.org/10.4061/2011/572689
103. McClure WR. Mechanism and control of transcription initiation in prokaryotes. Annu Rev Biochem 1985; 54:171-204; PMID:3896120; http://dx.doi.org/10.1146/annurev.bi.54.070185.001131
104. Steinmetz EJ, Warren CL, Kuehner JN, Panbehi B, Ansari AZ, Brow DA. Genome-wide distribution of yeast RNA polymerase II and its control by Sen1 helicase. Mol Cell 2006; 24:735-46; PMID:17157256; http://dx.doi.org/10.1016/j.molcel.2006.10.023
105. Kusuya Y, Kurokawa K, Ishikawa S, Ogasawara N, Oshima T. Transcription factor GreA contributes to resolving promoter-proximal pausing of RNA polymerase in Bacillus subtilis cells. J Bacteriol 2011; 193:3090-9; PMID:21515770; http://dx.doi.org/10.1128/JB.00086-11