4wqt Citations

The ratcheted and ratchetable structural states of RNA polymerase underlie multiple transcriptional functions.

Mol Cell 57 408-21 (2015)
Cited: 59 times
EuropePMC logo PMID: 25601758

Abstract

DNA-dependent RNA polymerase (RNAP) accomplishes multiple tasks during transcription by assuming different structural forms. Reportedly, the "tight" form performs nucleotide addition to nascent RNA, while the "ratcheted" form is adopted for transcription inhibition. In this study, we performed Cys-pair crosslinking (CPX) analyses of various transcription complexes of a bacterial RNAP and crystallographic analyses of its backtracked and Gre-factor-bound states to clarify which of the two forms is adopted. The ratcheted form was revealed to support GreA-dependent transcript cleavage, long backtracking, hairpin-dependent pausing, and termination. In contrast, the tight form correlated with nucleotide addition, mismatch-dependent pausing, one-nucleotide backtracking, and factor-independent transcript cleavage. RNAP in the paused/backtracked state, but not the nucleotide-addition state, readily transitions to the ratcheted form ("ratchetable"), indicating that the tight form represents two distinct regulatory states. The 3' end and the hairpin structure of the nascent RNA promote the ratchetable nature by modulating the trigger-loop conformation.

Reviews - 4wqt mentioned but not cited (1)

  1. Structural biology of bacterial RNA polymerase. Murakami KS. Biomolecules 5 848-864 (2015)

Articles - 4wqt mentioned but not cited (4)

  1. Allosteric Effector ppGpp Potentiates the Inhibition of Transcript Initiation by DksA. Molodtsov V, Sineva E, Zhang L, Huang X, Cashel M, Ades SE, Murakami KS. Mol Cell 69 828-839.e5 (2018)
  2. Dynamics of GreB-RNA polymerase interaction allow a proofreading accessory protein to patrol for transcription complexes needing rescue. Tetone LE, Friedman LJ, Osborne ML, Ravi H, Kyzer S, Stumper SK, Mooney RA, Landick R, Gelles J. Proc Natl Acad Sci U S A 114 E1081-E1090 (2017)
  3. In-Culture Cross-Linking of Bacterial Cells Reveals Large-Scale Dynamic Protein-Protein Interactions at the Peptide Level. de Jong L, de Koning EA, Roseboom W, Buncherd H, Wanner MJ, Dapic I, Jansen PJ, van Maarseveen JH, Corthals GL, Lewis PJ, Hamoen LW, de Koster CG. J Proteome Res 16 2457-2471 (2017)
  4. Conserved functions of the trigger loop and Gre factors in RNA cleavage by bacterial RNA polymerases. Miropolskaya N, Esyunina D, Kulbachinskiy A. J Biol Chem 292 6744-6752 (2017)


Reviews citing this publication (10)

  1. Mechanisms of Bacterial Transcription Termination: All Good Things Must End. Ray-Soni A, Bellecourt MJ, Landick R. Annu Rev Biochem 85 319-347 (2016)
  2. Mechanisms of Transcriptional Pausing in Bacteria. Kang JY, Mishanina TV, Landick R, Darst SA. J Mol Biol 431 4007-4029 (2019)
  3. The Mechanisms of Substrate Selection, Catalysis, and Translocation by the Elongating RNA Polymerase. Belogurov GA, Artsimovitch I. J Mol Biol 431 3975-4006 (2019)
  4. Controlling gene expression by DNA mechanics: emerging insights and challenges. Levens D, Baranello L, Kouzine F. Biophys Rev 8 259-268 (2016)
  5. Mechanisms of Stress Resistance and Gene Regulation in the Radioresistant Bacterium Deinococcus radiodurans. Agapov AA, Kulbachinskiy AV. Biochemistry (Mosc) 80 1201-1216 (2015)
  6. Transcription fidelity and its roles in the cell. Gamba P, Zenkin N. Curr Opin Microbiol 42 13-18 (2018)
  7. Protein Dynamics in F-like Bacterial Conjugation. Bragagnolo N, Rodriguez C, Samari-Kermani N, Fours A, Korouzhdehi M, Lysenko R, Audette GF. Biomedicines 8 E362 (2020)
  8. RNA polymerase pausing, stalling and bypass during transcription of damaged DNA: from molecular basis to functional consequences. Agapov A, Olina A, Kulbachinskiy A. Nucleic Acids Res 50 3018-3041 (2022)
  9. Architecture of the RNA polymerase II elongation complex: new insights into Spt4/5 and Elf1. Ehara H, Sekine SI. Transcription 9 286-291 (2018)
  10. Controlling gene expression by DNA mechanics: emerging insights and challenges. Levens D, Baranello L, Kouzine F. Biophys Rev 8 23-32 (2016)

Articles citing this publication (44)

  1. ppGpp Binding to a Site at the RNAP-DksA Interface Accounts for Its Dramatic Effects on Transcription Initiation during the Stringent Response. Ross W, Sanchez-Vazquez P, Chen AY, Lee JH, Burgos HL, Gourse RL. Mol Cell 62 811-823 (2016)
  2. Structure of the complete elongation complex of RNA polymerase II with basal factors. Ehara H, Yokoyama T, Shigematsu H, Yokoyama S, Shirouzu M, Sekine SI. Science 357 921-924 (2017)
  3. RNA Polymerase Accommodates a Pause RNA Hairpin by Global Conformational Rearrangements that Prolong Pausing. Kang JY, Mishanina TV, Bellecourt MJ, Mooney RA, Darst SA, Landick R. Mol Cell 69 802-815.e5 (2018)
  4. Structure of a transcribing RNA polymerase II-DSIF complex reveals a multidentate DNA-RNA clamp. Bernecky C, Plitzko JM, Cramer P. Nat Struct Mol Biol 24 809-815 (2017)
  5. ppGpp couples transcription to DNA repair in E. coli. Kamarthapu V, Epshtein V, Benjamin B, Proshkin S, Mironov A, Cashel M, Nudler E. Science 352 993-996 (2016)
  6. Structural basis of transcription arrest by coliphage HK022 Nun in an Escherichia coli RNA polymerase elongation complex. Kang JY, Olinares PD, Chen J, Campbell EA, Mustaev A, Chait BT, Gottesman ME, Darst SA. Elife 6 e25478 (2017)
  7. Structural Basis of Transcription: RNA Polymerase Backtracking and Its Reactivation. Abdelkareem M, Saint-André C, Takacs M, Papai G, Crucifix C, Guo X, Ortiz J, Weixlbaumer A. Mol Cell 75 298-309.e4 (2019)
  8. Structure of RNA polymerase I transcribing ribosomal DNA genes. Neyer S, Kunz M, Geiss C, Hantsche M, Hodirnau VV, Seybert A, Engel C, Scheffer MP, Cramer P, Frangakis AS. Nature 540 607-610 (2016)
  9. Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex. Malone B, Chen J, Wang Q, Llewellyn E, Choi YJ, Olinares PDB, Cao X, Hernandez C, Eng ET, Chait BT, Shaw DE, Landick R, Darst SA, Campbell EA. Proc Natl Acad Sci U S A 118 e2102516118 (2021)
  10. Widespread Backtracking by RNA Pol II Is a Major Effector of Gene Activation, 5' Pause Release, Termination, and Transcription Elongation Rate. Sheridan RM, Fong N, D'Alessandro A, Bentley DL. Mol Cell 73 107-118.e4 (2019)
  11. Dynamic turnover of paused Pol II complexes at human promoters. Erickson B, Sheridan RM, Cortazar M, Bentley DL. Genes Dev 32 1215-1225 (2018)
  12. TFE and Spt4/5 open and close the RNA polymerase clamp during the transcription cycle. Schulz S, Gietl A, Smollett K, Tinnefeld P, Werner F, Grohmann D. Proc Natl Acad Sci U S A 113 E1816-25 (2016)
  13. Biochemical Analysis of Yeast Suppressor of Ty 4/5 (Spt4/5) Reveals the Importance of Nucleic Acid Interactions in the Prevention of RNA Polymerase II Arrest. Crickard JB, Fu J, Reese JC. J Biol Chem 291 9853-9870 (2016)
  14. NusG inhibits RNA polymerase backtracking by stabilizing the minimal transcription bubble. Turtola M, Belogurov GA. Elife 5 e18096 (2016)
  15. The elemental mechanism of transcriptional pausing. Saba J, Chua XY, Mishanina TV, Nayak D, Windgassen TA, Mooney RA, Landick R. Elife 8 e40981 (2019)
  16. Trigger loop of RNA polymerase is a positional, not acid-base, catalyst for both transcription and proofreading. Mishanina TV, Palo MZ, Nayak D, Mooney RA, Landick R. Proc Natl Acad Sci U S A 114 E5103-E5112 (2017)
  17. High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop. Qiu C, Erinne OC, Dave JM, Cui P, Jin H, Muthukrishnan N, Tang LK, Babu SG, Lam KC, Vandeventer PJ, Strohner R, Van den Brulle J, Sze SH, Kaplan CD. PLoS Genet 12 e1006321 (2016)
  18. CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition. Bae B, Nayak D, Ray A, Mustaev A, Landick R, Darst SA. Proc Natl Acad Sci U S A 112 E4178-87 (2015)
  19. Pause sequences facilitate entry into long-lived paused states by reducing RNA polymerase transcription rates. Gabizon R, Lee A, Vahedian-Movahed H, Ebright RH, Bustamante CJ. Nat Commun 9 2930 (2018)
  20. TFS and Spt4/5 accelerate transcription through archaeal histone-based chromatin. Sanders TJ, Lammers M, Marshall CJ, Walker JE, Lynch ER, Santangelo TJ. Mol Microbiol 111 784-797 (2019)
  21. Lineage-specific variations in the trigger loop modulate RNA proofreading by bacterial RNA polymerases. Esyunina D, Turtola M, Pupov D, Bass I, Klimašauskas S, Belogurov G, Kulbachinskiy A. Nucleic Acids Res 44 1298-1308 (2016)
  22. RNA Polymerase Clamp Movement Aids Dissociation from DNA but Is Not Required for RNA Release at Intrinsic Terminators. Bellecourt MJ, Ray-Soni A, Harwig A, Mooney RA, Landick R. J Mol Biol 431 696-713 (2019)
  23. Real-Time Observation of Backtracking by Bacterial RNA Polymerase. Lass-Napiorkowska A, Heyduk T. Biochemistry 55 647-658 (2016)
  24. Regulation of transcriptional pausing through the secondary channel of RNA polymerase. Esyunina D, Agapov A, Kulbachinskiy A. Proc Natl Acad Sci U S A 113 8699-8704 (2016)
  25. Interplay between σ region 3.2 and secondary channel factors during promoter escape by bacterial RNA polymerase. Petushkov I, Esyunina D, Mekler V, Severinov K, Pupov D, Kulbachinskiy A. Biochem J 474 4053-4064 (2017)
  26. High intrinsic hydrolytic activity of cyanobacterial RNA polymerase compensates for the absence of transcription proofreading factors. Riaz-Bradley A, James K, Yuzenkova Y. Nucleic Acids Res 48 1341-1352 (2020)
  27. Obligate movements of an active site-linked surface domain control RNA polymerase elongation and pausing via a Phe pocket anchor. Bao Y, Landick R. Proc Natl Acad Sci U S A 118 e2101805118 (2021)
  28. Purification and Characterization of Recombinant Deinococcus radiodurans RNA Polymerase. Esyunina DM, Kulbachinskiy AV. Biochemistry (Mosc) 80 1271-1278 (2015)
  29. Active site closure stabilizes the backtracked state of RNA polymerase. Turtola M, Mäkinen JJ, Belogurov GA. Nucleic Acids Res 46 10870-10887 (2018)
  30. Intrinsic Cleavage of RNA Polymerase II Adopts a Nucleobase-independent Mechanism Assisted by Transcript Phosphate. Ka Man Tse C, Xu J, Xu L, Sheong FK, Wang S, Chow HY, Gao X, Li X, Cheung PP, Wang D, Zhang Y, Huang X. Nat Energy 2 228-235 (2019)
  31. A structure-based kinetic model of transcription. Zuo Y, Steitz TA. Transcription 8 1-8 (2017)
  32. Gfh factors and NusA cooperate to stimulate transcriptional pausing and termination. Agapov A, Olina A, Esyunina D, Kulbachinskiy A. FEBS Lett 591 946-953 (2017)
  33. Gre-family factors modulate DNA damage sensing by Deinococcus radiodurans RNA polymerase. Agapov A, Esyunina D, Kulbachinskiy A. RNA Biol 16 1711-1720 (2019)
  34. Oxazinomycin arrests RNA polymerase at the polythymidine sequences. Prajapati RK, Rosenqvist P, Palmu K, Mäkinen JJ, Malinen AM, Virta P, Metsä-Ketelä M, Belogurov GA. Nucleic Acids Res 47 10296-10312 (2019)
  35. Ratcheting of RNA polymerase toward structural principles of RNA polymerase operations. Sekine S, Murayama Y, Svetlov V, Nudler E, Yokoyama S. Transcription 6 56-60 (2015)
  36. A Thermus phage protein inhibits host RNA polymerase by preventing template DNA strand loading during open promoter complex formation. Ooi WY, Murayama Y, Mekler V, Minakhin L, Severinov K, Yokoyama S, Sekine SI. Nucleic Acids Res 46 431-441 (2018)
  37. Conserved Trigger Loop Histidine of RNA Polymerase II Functions as a Positional Catalyst Primarily through Steric Effects. Palo MZ, Zhu J, Mishanina TV, Landick R. Biochemistry 60 3323-3336 (2021)
  38. Hinge action versus grip in translocation by RNA polymerase. Nedialkov YA, Opron K, Caudill HL, Assaf F, Anderson AJ, Cukier RI, Wei G, Burton ZF. Transcription 9 1-16 (2018)
  39. An ensemble of interconverting conformations of the elemental paused transcription complex creates regulatory options. Kang JY, Mishanina TV, Bao Y, Chen J, Llewellyn E, Liu J, Darst SA, Landick R. Proc Natl Acad Sci U S A 120 e2215945120 (2023)
  40. A trailing ribosome speeds up RNA polymerase at the expense of transcript fidelity via force and allostery. Wee LM, Tong AB, Florez Ariza AJ, Cañari-Chumpitaz C, Grob P, Nogales E, Bustamante CJ. Cell 186 1244-1262.e34 (2023)
  41. Dynamics of bridge helix bending in RNA polymerase II. Wang ZF, Fu YB, Wang PY, Xie P. Proteins 85 614-629 (2017)
  42. Structural basis of the transcription termination factor Rho engagement with transcribing RNA polymerase from Thermus thermophilus. Murayama Y, Ehara H, Aoki M, Goto M, Yokoyama T, Sekine SI. Sci Adv 9 eade7093 (2023)
  43. Role of the trigger loop in translesion RNA synthesis by bacterial RNA polymerase. Agapov A, Ignatov A, Turtola M, Belogurov G, Esyunina D, Kulbachinskiy A. J Biol Chem 295 9583-9595 (2020)
  44. Structural and functional basis of the universal transcription factor NusG pro-pausing activity in Mycobacterium tuberculosis. Delbeau M, Omollo EO, Froom R, Koh S, Mooney RA, Lilic M, Brewer JJ, Rock J, Darst SA, Campbell EA, Landick R. Mol Cell 83 1474-1488.e8 (2023)