The Spt4-Spt5 complex: a multi-faceted regulator of transcription elongation.

In all domains of life, elongating RNA polymerases require the assistance of accessory factors to maintain their processivity and regulate their rate. Among these elongation factors, the Spt5/NusG factors stand out. Members of this protein family appear to be the only transcription accessory proteins that are universally conserved across all domains of life. In archaea and eukaryotes, Spt5 associates with a second protein, Spt4. In addition to regulating elongation, the eukaryotic Spt4-Spt5 complex appears to couple chromatin modification states and RNA processing to transcription elongation. This review discusses the experimental bases for our current understanding of Spt4-Spt5 function and recent studies that are beginning to elucidate the structure of Spt4-Spt5/RNA polymerase complexes and mechanism of Spt4-Spt5 action. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation.

[1]  Yang Shi,et al.  CDK-9/cyclin T (P-TEFb) is required in two postinitiation pathways for transcription in the C. elegans embryo. , 2002, Genes & development.

[2]  F. Winston,et al.  SPT4, SPT5 and SPT6 interactions: effects on transcription and viability in Saccharomyces cerevisiae. , 1992, Genetics.

[3]  H. Handa,et al.  Locus-Specific Requirements for Spt5 in Transcriptional Activation and Repression in Drosophila , 2004, Current Biology.

[4]  P. Cramer,et al.  Architecture of the RNA Polymerase II-TFIIS Complex and Implications for mRNA Cleavage , 2003, Cell.

[5]  Kyu-Jin Park,et al.  Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. , 2003, Molecular cell.

[6]  C. Squires,et al.  Antiterminator‐dependent modulation of transcription elongation rates by NusB and NusG , 1999, Molecular microbiology.

[7]  D. Bentley,et al.  RNA polymerase II pauses and associates with pre-mRNA processing factors at both ends of genes , 2008, Nature Structural &Molecular Biology.

[8]  Craig D. Kaplan,et al.  Interaction between Transcription Elongation Factors and mRNA 3′-End Formation at the Saccharomyces cerevisiae GAL10-GAL7 Locus* , 2005, Journal of Biological Chemistry.

[9]  G. Hartzog,et al.  Histone H3K4 and K36 Methylation, Chd1 and Rpd3S Oppose the Functions of Saccharomyces cerevisiae Spt4–Spt5 in Transcription , 2010, Genetics.

[10]  Carl Wu,et al.  The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo. , 2000, Molecular cell.

[11]  P. Cramer,et al.  Structural Basis of Transcription: An RNA Polymerase II Elongation Complex at 3.3 Å Resolution , 2001, Science.

[12]  D. Price,et al.  Flavopiridol Inactivates P-TEFb and Blocks Most RNA Polymerase II Transcription in Vivo * , 2001, The Journal of Biological Chemistry.

[13]  R. Conaway,et al.  Roles for both the RAP30 and RAP74 subunits of transcription factor IIF in transcription initiation and elongation by RNA polymerase II. , 1994, The Journal of biological chemistry.

[14]  Denys A. Khaperskyy,et al.  Functions of Saccharomyces cerevisiae TFIIF during Transcription Start Site Utilization , 2008, Molecular and Cellular Biology.

[15]  L. Jansen,et al.  Transcription elongation factor Spt4 mediates loss of phosphorylated RNA polymerase II transcription in response to DNA damage. , 2002, Nucleic acids research.

[16]  Denys A. Khaperskyy,et al.  A Functional Role for the Switch 2 Region of Yeast RNA Polymerase II in Transcription Start Site Utilization and Abortive Initiation* , 2005, Journal of Biological Chemistry.

[17]  R. Young,et al.  Functional association of Gdown1 with RNA polymerase II poised on human genes. , 2012, Molecular cell.

[18]  Sohail Malik,et al.  Transcriptional regulation by Pol II(G) involving mediator and competitive interactions of Gdown1 and TFIIF with Pol II. , 2012, Molecular cell.

[19]  P. Farnham,et al.  Myc Recruits P-TEFb to Mediate the Final Step in the Transcriptional Activation of the cad Promoter* , 2002, The Journal of Biological Chemistry.

[20]  Steven Hahn,et al.  The Acidic Transcription Activator Gcn4 Binds the Mediator Subunit Gal11/med15 Using a Simple Protein Interface Forming a Fuzzy Complex , 2022 .

[21]  D. Gilmour,et al.  Analysis of Polymerase II Elongation Complexes by Native Gel Electrophoresis , 2004, Journal of Biological Chemistry.

[22]  T. Rana,et al.  Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5 , 2004, Retrovirology.

[23]  Paul W. Sternberg,et al.  RNA Pol II Accumulates at Promoters of Growth Genes During Developmental Arrest , 2009, Science.

[24]  Hiroshi Handa,et al.  Elongation Inhibition by DRB Sensitivity-Inducing Factor Is Regulated by the A20 Promoter via a Novel Negative Element and NF-κB , 2004, Molecular and Cellular Biology.

[25]  Hiroshi Handa,et al.  Differential Regulation of NF-κB by Elongation Factors Is Determined by Core Promoter Type , 2007, Molecular and Cellular Biology.

[26]  P. Cramer,et al.  Complete RNA polymerase II elongation complex structure and its interactions with NTP and TFIIS. , 2004, Molecular cell.

[27]  S. Hahn,et al.  Position of the general transcription factor TFIIF within the RNA polymerase II transcription preinitiation complex , 2010, The EMBO journal.

[28]  Kevin Struhl,et al.  Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo. , 2005, Molecular cell.

[29]  G. Fink,et al.  Mutations affecting Ty-mediated expression of the HIS4 gene of Saccharomyces cerevisiae. , 1984, Genetics.

[30]  Karen Zhou,et al.  Control of transcriptional elongation and cotranscriptional histone modification by the yeast BUR kinase substrate Spt5 , 2009, Proceedings of the National Academy of Sciences.

[31]  D. Luse,et al.  Newly Initiated RNA Encounters a Factor Involved in Splicing Immediately upon Emerging from within RNA Polymerase II* , 2004, Journal of Biological Chemistry.

[32]  R. Landick,et al.  Pausing by bacterial RNA polymerase is mediated by mechanistically distinct classes of signals. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[33]  A. Shatkin,et al.  Transcription elongation factor hSPT5 stimulates mRNA capping. , 1999, Genes & development.

[34]  J. Greenblatt,et al.  NusG, a new Escherichia coli elongation factor involved in transcriptional antitermination by the N protein of phage lambda. , 1992, The Journal of biological chemistry.

[35]  S. Squazzo,et al.  The Paf1 complex physically and functionally associates with transcription elongation factors in vivo , 2002, The EMBO journal.

[36]  Takashi Okamoto,et al.  c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis , 2003, Oncogene.

[37]  D. Gilmour,et al.  Interactions between DSIF (DRB sensitivity inducing factor), NELF (negative elongation factor), and the Drosophila RNA polymerase II transcription elongation complex , 2010, Proceedings of the National Academy of Sciences.

[38]  F. Spencer,et al.  Faithful chromosome transmission requires Spt4p, a putative regulator of chromatin structure in Saccharomyces cerevisiae , 1996, Molecular and cellular biology.

[39]  N. Pace,et al.  The genetic core of the universal ancestor. , 2003, Genome research.

[40]  M. Gottesman,et al.  Escherichia coli NusG protein stimulates transcription elongation rates in vivo and in vitro , 1995, Journal of bacteriology.

[41]  Stanley N Cohen,et al.  Spt4 Is Selectively Required for Transcription of Extended Trinucleotide Repeats , 2012, Cell.

[42]  Yael Mandel-Gutfreund,et al.  Exploring functional relationships between components of the gene expression machinery , 2005, Nature Structural &Molecular Biology.

[43]  A. Hinnebusch,et al.  The Spt4p Subunit of Yeast DSIF Stimulates Association of the Paf1 Complex with Elongating RNA Polymerase II , 2006, Molecular and Cellular Biology.

[44]  C. Denis,et al.  In Vivo Evidence that Defects in the Transcriptional Elongation Factors RPB2, TFIIS, and SPT5 Enhance Upstream Poly(A) Site Utilization , 2003, Molecular and Cellular Biology.

[45]  Mahadeb Pal,et al.  The initiation–elongation transition: Lateral mobility of RNA in RNA polymerase II complexes is greatly reduced at +8/+9 and absent by +23 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[46]  K. Struhl,et al.  A new class of activation-defective TATA-binding protein mutants: evidence for two steps of transcriptional activation in vivo , 1996, Molecular and cellular biology.

[47]  C. Kane,et al.  Promoting elongation with transcript cleavage stimulatory factors. , 2002, Biochimica et biophysica acta.

[48]  P. Tompa,et al.  Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. , 2008, Trends in biochemical sciences.

[49]  D. Taatjes,et al.  The human Mediator complex: a versatile, genome-wide regulator of transcription. , 2010, Trends in biochemical sciences.

[50]  Stewart Shuman,et al.  Interactions between Fission Yeast mRNA Capping Enzymes and Elongation Factor Spt5* , 2002, The Journal of Biological Chemistry.

[51]  E. Cho,et al.  mRNA Capping Enzyme Activity Is Coupled to an Early Transcription Elongation , 2004, Molecular and Cellular Biology.

[52]  D. Price,et al.  Functional analysis of Drosophila factor 5 (TFIIF), a general transcription factor. , 1994, The Journal of biological chemistry.

[53]  S. Malik,et al.  Identification of a regulator of transcription elongation as an accessory factor for the human Mediator coactivator , 2007, Proceedings of the National Academy of Sciences.

[54]  Claire Picart,et al.  RNA‐directed DNA methylation requires an AGO4‐interacting member of the SPT5 elongation factor family , 2009, EMBO reports.

[55]  J. Karn,et al.  Spt5 Cooperates with Human Immunodeficiency Virus Type 1 Tat by Preventing Premature RNA Release at Terminator Sequences , 2002, Molecular and Cellular Biology.

[56]  F. Werner,et al.  Evolution of multisubunit RNA polymerases in the three domains of life , 2011, Nature Reviews Microbiology.

[57]  W. Webb,et al.  P-TEFb Is Critical for the Maturation of RNA Polymerase II into Productive Elongation In Vivo , 2007, Molecular and Cellular Biology.

[58]  C P Ponting,et al.  Tudor domains in proteins that interact with RNA. , 1997, Trends in biochemical sciences.

[59]  Craig D. Kaplan,et al.  A Dual Interface Determines the Recognition of RNA Polymerase II by RNA Capping Enzyme* , 2010, The Journal of Biological Chemistry.

[60]  H. Handa,et al.  A regulator of transcriptional elongation controls vertebrate neuronal development , 2000, Nature.

[61]  Patrick Cramer,et al.  Architecture of the RNA polymerase–Spt4/5 complex and basis of universal transcription processivity , 2011, The EMBO journal.

[62]  D. Price,et al.  Analysis of factor interactions with RNA polymerase II elongation complexes using a new electrophoretic mobility shift assay , 2008, Nucleic acids research.

[63]  J. Lis,et al.  High-resolution localization of Drosophila Spt5 and Spt6 at heat shock genes in vivo: roles in promoter proximal pausing and transcription elongation. , 2000, Genes & development.

[64]  P. Laybourn,et al.  RNA polymerase II and TBP occupy the repressed CYC1 promoter , 2001, Molecular microbiology.

[65]  J. Chen,et al.  Binding of TFIID to the CYC1 TATA boxes in yeast occurs independently of upstream activating sequences. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[66]  T. Hughes,et al.  BUR Kinase Selectively Regulates H3 K4 Trimethylation and H2B Ubiquitylation through Recruitment of the PAF Elongation Complex , 2005, Current Biology.

[67]  Bin Xie,et al.  Pausing of RNA Polymerase II Disrupts DNA-Specified Nucleosome Organization to Enable Precise Gene Regulation , 2010, Cell.

[68]  D. Vassylyev,et al.  Allosteric control of the RNA polymerase by the elongation factor RfaH , 2007, Nucleic acids research.

[69]  K. Adelman,et al.  Coupling polymerase pausing and chromatin landscapes for precise regulation of transcription. , 2012, Biochimica et biophysica acta.

[70]  Sunyoung Kim,et al.  Role of Mediator in Regulating Pol II Elongation and Nucleosome Displacement in Saccharomyces cerevisiae , 2012, Genetics.

[71]  Daniel F Tardiff,et al.  Protein characterization of Saccharomyces cerevisiae RNA polymerase II after in vivo cross-linking , 2007, Proceedings of the National Academy of Sciences.

[72]  J. R. Morris,et al.  Spt5 and spt6 are associated with active transcription and have characteristics of general elongation factors in D. melanogaster. , 2000, Genes & development.

[73]  Nicholas Proudfoot,et al.  Isw1 Chromatin Remodeling ATPase Coordinates Transcription Elongation and Termination by RNA Polymerase II , 2003, Cell.

[74]  Mark Johnston,et al.  The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS. , 2005, Molecular cell.

[75]  H. Handa,et al.  Structure–function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex , 2003, Genes to cells : devoted to molecular & cellular mechanisms.

[76]  F. Lacroute,et al.  6-Azauracil inhibition of GTP biosynthesis in Saccharomyces cerevisiae , 1992, Current Genetics.

[77]  S. Buratowski,et al.  Npl3 is an antagonist of mRNA 3′ end formation by RNA polymerase II , 2005, The EMBO journal.

[78]  A. Ansari,et al.  Regulator trafficking on bacterial transcription units in vivo. , 2009, Molecular cell.

[79]  I. Artsimovitch,et al.  Functional regions of the N-terminal domain of the antiterminator RfaH , 2010, Molecular microbiology.

[80]  Michael Shales,et al.  Extensive homology among the largest subunits of eukaryotic and prokaryotic RNA polymerases , 1985, Cell.

[81]  K. Yano,et al.  Human Transcription Elongation Factor NELF: Identification of Novel Subunits and Reconstitution of the Functionally Active Complex , 2003, Molecular and Cellular Biology.

[82]  Chun-Hsiung Wang,et al.  Regulation of mammalian transcription by Gdown1 through a novel steric crosstalk revealed by cryo‐EM , 2012, The EMBO journal.

[83]  S. Yokoyama,et al.  Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 Å resolution , 2002, Nature.

[84]  S. Hahn,et al.  The positions of TFIIF and TFIIE in the RNA polymerase II transcription preinitiation complex , 2007, Nature Structural &Molecular Biology.

[85]  A. Wierzbicki,et al.  Independent Chromatin Binding of ARGONAUTE4 and SPT5L/KTF1 Mediates Transcriptional Gene Silencing , 2011, PLoS genetics.

[86]  F. Werner,et al.  RNAP subunits F/E (RPB4/7) are stably associated with archaeal RNA polymerase: using fluorescence anisotropy to monitor RNAP assembly in vitro. , 2009, The Biochemical journal.

[87]  F. Winston,et al.  SPT5, an essential gene important for normal transcription in Saccharomyces cerevisiae, encodes an acidic nuclear protein with a carboxy-terminal repeat , 1991, Molecular and cellular biology.

[88]  A. Edwards,et al.  Intrinsic Transcript Cleavage in Yeast RNA Polymerase II Elongation Complexes* , 2003, Journal of Biological Chemistry.

[89]  F. Winston,et al.  Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. , 1998, Genes & development.

[90]  Hiroshi Handa,et al.  NELF, a Multisubunit Complex Containing RD, Cooperates with DSIF to Repress RNA Polymerase II Elongation , 1999, Cell.

[91]  Patrick Cramer,et al.  The Spt5 C-Terminal Region Recruits Yeast 3′ RNA Cleavage Factor I , 2012, Molecular and Cellular Biology.

[92]  D. Schneider,et al.  Yeast Transcription Elongation Factor Spt5 Associates with RNA Polymerase I and RNA Polymerase II Directly* , 2011, The Journal of Biological Chemistry.

[93]  Vasco M. Barreto,et al.  Activation-Induced Cytidine Deaminase Targets DNA at Sites of RNA Polymerase II Stalling by Interaction with Spt5 , 2010, Cell.

[94]  Tahir H. Tahirov,et al.  Structural basis for transcription elongation by bacterial RNA polymerase , 2007, Nature.

[95]  Joyce Li,et al.  Elongation factor NusG interacts with termination factor rho to regulate termination and antitermination of transcription. , 1993, Genes & development.

[96]  P. Cramer,et al.  Structural basis of RNA polymerase II backtracking, arrest and reactivation , 2011, Nature.

[97]  S. Shuman,et al.  Separable Functions of the Fission Yeast Spt5 Carboxyl-Terminal Domain (CTD) in Capping Enzyme Binding and Transcription Elongation Overlap with Those of the RNA Polymerase II CTD , 2010, Molecular and Cellular Biology.

[98]  Hien G. Tran,et al.  Chromatin remodeling protein Chd1 interacts with transcription elongation factors and localizes to transcribed genes , 2003, The EMBO journal.

[99]  R. Gaynor,et al.  Domains in the SPT5 Protein That Modulate Its Transcriptional Regulatory Properties , 2000, Molecular and Cellular Biology.

[100]  M. Teng,et al.  Crystal structure of NusG N‐terminal (NGN) domain from Methanocaldococcus jannaschii and its interaction with rpoE″ , 2009, Proteins.

[101]  R. Ho,et al.  The elongation factors Pandora/Spt6 and Foggy/Spt5 promote transcription in the zebrafish embryo. , 2002, Development.

[102]  D. Lindstrom,et al.  Genetic interactions of Spt4-Spt5 and TFIIS with the RNA polymerase II CTD and CTD modifying enzymes in Saccharomyces cerevisiae. , 2001, Genetics.

[103]  K. Murakami,et al.  RNA polymerase and transcription elongation factor Spt4/5 complex structure , 2010, Proceedings of the National Academy of Sciences.

[104]  A. Mustaev,et al.  Transcription elongation complex: structure and function. , 2001, Current opinion in microbiology.

[105]  R. Guérois,et al.  The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding. , 2004, Structure.

[106]  Alexandra M. E. Jones,et al.  An atypical RNA polymerase involved in RNA silencing shares small subunits with RNA polymerase II , 2009, Nature Structural &Molecular Biology.

[107]  D. Lafontaine,et al.  A Functional Interface at the rDNA Connects rRNA Synthesis, Pre-rRNA Processing and Nucleolar Surveillance in Budding Yeast , 2011, PloS one.

[108]  Steven Hahn,et al.  Phosphorylation of the Transcription Elongation Factor Spt5 by Yeast Bur1 Kinase Stimulates Recruitment of the PAF Complex , 2009, Molecular and Cellular Biology.

[109]  D. Bentley,et al.  "Cotranscriptionality": the transcription elongation complex as a nexus for nuclear transactions. , 2009, Molecular cell.

[110]  Jean Yee Hwa Yang,et al.  Analysis of a Splice Array Experiment Elucidates Roles of Chromatin Elongation Factor Spt4–5 in Splicing , 2005, PLoS Comput. Biol..

[111]  D. Luse,et al.  Transcription on nucleosomal templates by RNA polymerase II in vitro: inhibition of elongation with enhancement of sequence-specific pausing. , 1991, Genes & development.

[112]  D. Luse,et al.  Factor-stimulated RNA polymerase II transcribes at physiological elongation rates on naked DNA but very poorly on chromatin templates. , 1992, The Journal of biological chemistry.

[113]  J R Yates,et al.  RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing , 2006, Proceedings of the National Academy of Sciences.

[114]  M. Nomura,et al.  The Transcription Elongation Factor Spt5 Influences Transcription by RNA Polymerase I Positively and Negatively* , 2011, The Journal of Biological Chemistry.

[115]  J. Yates,et al.  Dual Roles for Spt5 in Pre-mRNA Processing and Transcription Elongation Revealed by Identification of Spt5-Associated Proteins , 2003, Molecular and Cellular Biology.

[116]  Andrew C. R. Martin,et al.  Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif , 2010, Nucleic acids research.

[117]  Björn M. Burmann,et al.  A NusE:NusG Complex Links Transcription and Translation , 2010, Science.

[118]  Jena Yamada,et al.  Core structure of the yeast spt4-spt5 complex: a conserved module for regulation of transcription elongation. , 2008, Structure.

[119]  R. Landick,et al.  The Transcriptional Regulator RfaH Stimulates RNA Chain Synthesis after Recruitment to Elongation Complexes by the Exposed Nontemplate DNA Strand , 2002, Cell.

[120]  Pierre-Étienne Jacques,et al.  DSIF and RNA Polymerase II CTD Phosphorylation Coordinate the Recruitment of Rpd3S to Actively Transcribed Genes , 2010, PLoS genetics.

[121]  Richard A Young,et al.  Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. , 2002, Molecular cell.

[122]  R. Burgess,et al.  Mutational Analysis of β′260–309, a ς70 Binding Site Located on Escherichia coliCore RNA Polymerase* , 2000, The Journal of Biological Chemistry.

[123]  T. Honjo,et al.  The DSIF Subunits Spt4 and Spt5 Have Distinct Roles at Various Phases of Immunoglobulin Class Switch Recombination , 2012, PLoS genetics.

[124]  P. Cramer,et al.  Structural Basis of Transcription: RNA Polymerase II at 2.8 Ångstrom Resolution , 2001, Science.

[125]  H. Handa,et al.  DSIF contributes to transcriptional activation by DNA-binding activators by preventing pausing during transcription elongation , 2007, Nucleic acids research.

[126]  T. Rana,et al.  DSIF and NELF Interact with RNA Polymerase II Elongation Complex and HIV-1 Tat Stimulates P-TEFb-mediated Phosphorylation of RNA Polymerase II and DSIF during Transcription Elongation* , 2001, The Journal of Biological Chemistry.

[127]  F. Winston,et al.  Molecular and genetic characterization of SPT4, a gene important for transcription initiation in Saccharomyces cerevisiae , 1993, Molecular and General Genetics MGG.

[128]  Jianhua Fu,et al.  Mutual remodeling and conformation grid: a mediator code? , 2012, Structure.

[129]  L. Jansen,et al.  Spt4 modulates Rad26 requirement in transcription‐coupled nucleotide excision repair , 2000, The EMBO journal.

[130]  J. Jaehning,et al.  The Paf1 complex: platform or player in RNA polymerase II transcription? , 2010, Biochimica et biophysica acta.

[131]  M. Levitt,et al.  Structural Basis of Transcription: Backtracked RNA Polymerase II at 3.4 Angstrom Resolution , 2009, Science.

[132]  F. Werner.  A Nexus for Gene Expression—Molecular Mechanisms of Spt5 and NusG in the Three Domains of Life , 2012, Journal of molecular biology.

[133]  John T. Lis,et al.  Breaking barriers to transcription elongation , 2006, Nature Reviews Molecular Cell Biology.

[134]  T. Lagrange,et al.  Plant-specific multisubunit RNA polymerase in gene silencing , 2010, Epigenetics.

[135]  D. Luse,et al.  Promoter Clearance by RNA Polymerase II Is an Extended, Multistep Process Strongly Affected by Sequence , 2001, Molecular and Cellular Biology.

[136]  Vasily M Studitsky,et al.  Nature of the nucleosomal barrier to RNA polymerase II. , 2005, Molecular cell.

[137]  Philip Lijnzaad,et al.  Genome-wide analyses reveal RNA polymerase II located upstream of genes poised for rapid response upon S. cerevisiae stationary phase exit. , 2005, Molecular cell.

[138]  F. Winston,et al.  Identification and analysis of a functional human homolog of the SPT4 gene of Saccharomyces cerevisiae , 1996, Molecular and cellular biology.

[139]  R. Landick,et al.  The β subunit gate loop is required for RNA polymerase modification by RfaH and NusG. , 2011, Molecular cell.

[140]  S. Shuman,et al.  Characterization of the Schizosaccharomyces pombe Cdk9/Pch1 Protein Kinase , 2003, Journal of Biological Chemistry.

[141]  A. Shilatifard,et al.  Human Mediator Subunit MED26 Functions as a Docking Site for Transcription Elongation Factors , 2011, Cell.

[142]  Hailing Jin,et al.  An Effector of RNA-Directed DNA Methylation in Arabidopsis Is an ARGONAUTE 4- and RNA-Binding Protein , 2009, Cell.

[143]  C. Guthrie,et al.  Identification of novel genes required for yeast pre-mRNA splicing by means of cold-sensitive mutations. , 1996, Genetics.

[144]  L. A. Stargell,et al.  Activation of a Poised RNAPII-Dependent Promoter Requires Both SAGA and Mediator , 2010, Genetics.

[145]  R. Gaynor,et al.  Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat-activation. , 1998, Journal of molecular biology.

[146]  P. Sharp,et al.  5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits transcription elongation by RNA polymerase II in vitro. , 1989, The Journal of biological chemistry.

[147]  Shisheng Li,et al.  The C-terminal Repeat Domain of Spt5 Plays an Important Role in Suppression of Rad26-independent Transcription Coupled Repair* , 2009, The Journal of Biological Chemistry.

[148]  Hiroshi Handa,et al.  P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation. , 2006, Molecular cell.

[149]  A. Shilatifard.  Transcriptional elongation control by RNA polymerase II: a new frontier. , 2004, Biochimica et biophysica acta.

[150]  Christopher C. Ebmeier,et al.  CDK8 is a positive regulator of transcriptional elongation within the serum response network , 2010, Nature Structural &Molecular Biology.

[151]  Bryan J Venters,et al.  A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome , 2008, Genome research.

[152]  R. Landick,et al.  Two structurally independent domains of E. coli NusG create regulatory plasticity via distinct interactions with RNA polymerase and regulators. , 2009, Journal of molecular biology.

[153]  H. Handa,et al.  A Highly Purified RNA Polymerase II Elongation Control System* , 2001, The Journal of Biological Chemistry.

[154]  C. Ponting.  Novel domains and orthologues of eukaryotic transcription elongation factors. , 2002, Nucleic acids research.

[155]  K. Schweimer,et al.  The small hSpt4 subunit of the human transcription elongation factor DSIF is a Zn-finger protein with alpha/beta type topology. , 2008, Biochemical and biophysical research communications.

[156]  Y. Nedialkov,et al.  A Key Role for the α1 Helix of Human RAP74 in the Initiation and Elongation of RNA Chains* , 2002, The Journal of Biological Chemistry.

[157]  Pascal Chartrand,et al.  Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to the yeast bud. , 2010, Genes & development.

[158]  Paul Rösch,et al.  Crystal structure of the human transcription elongation factor DSIF hSpt4 subunit in complex with the hSpt5 dimerization interface. , 2010, The Biochemical journal.

[159]  Nick V Grishin,et al.  Structural basis for converting a general transcription factor into an operon-specific virulence regulator. , 2007, Molecular cell.

[160]  M. Basrai,et al.  Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae , 2004, The EMBO journal.

[161]  A. Aguilera,et al.  Molecular evidence for a positive role of Spt4 in transcription elongation , 2003, The EMBO journal.

[162]  H. Handa,et al.  Structure and Function of the Human Transcription Elongation Factor DSIF* , 1999, The Journal of Biological Chemistry.

[163]  H. Handa,et al.  DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation. , 2009, Genes & development.

[164]  Christopher B. Burge,et al.  c-Myc Regulates Transcriptional Pause Release , 2010, Cell.

[165]  D. Vassylyev,et al.  The elongation factor RfaH and the initiation factor σ bind to the same site on the transcription elongation complex , 2008, Proceedings of the National Academy of Sciences.

[166]  Craig D. Kaplan,et al.  Competing for the clamp: promoting RNA polymerase processivity and managing the transition from initiation to elongation. , 2011, Molecular cell.

[167]  M. Rudd,et al.  The active site of RNA polymerase II participates in transcript cleavage within arrested ternary complexes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[168]  D. Price,et al.  Properties of RNA Polymerase II Elongation Complexes Before and After the P-TEFb-mediated Transition into Productive Elongation* , 2007, Journal of Biological Chemistry.

[169]  K. Yano,et al.  DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. , 1998, Genes & development.

[170]  C. Burns,et al.  Combinatorial effects of NusA and NusG on transcription elongation and Rho-dependent termination in Escherichia coli. , 1998, Journal of molecular biology.

[171]  Liat Amir-Zilberstein,et al.  Interplay between E-box and NF-κB in Regulation of A20 Gene by DRB Sensitivity-inducing Factor (DSIF)* , 2008, Journal of Biological Chemistry.

[172]  B. Peterlin,et al.  Controlling the elongation phase of transcription with P-TEFb. , 2006, Molecular cell.

[173]  Johannes Söding,et al.  Uniform transitions of the general RNA polymerase II transcription complex , 2010, Nature Structural &Molecular Biology.

[174]  J. Lis,et al.  The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila , 2002, Nature.