Gene Symbol: SPT4
Description: transcription elongation factor SPT4
Alias: transcription elongation factor SPT4
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Braun M, Costa P, Crisucci E, Arndt K. Identification of Rkr1, a nuclear RING domain protein with functional connections to chromatin modification in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:2800-11 pubmed
    ..Taken together, our results identify a new participant in a protein ubiquitylation pathway within the nucleus that acts to modulate chromatin function and transcription. ..
  2. Tous C, Rondon A, Garcia Rubio M, González Aguilera C, Luna R, Aguilera A. A novel assay identifies transcript elongation roles for the Nup84 complex and RNA processing factors. EMBO J. 2011;30:1953-64 pubmed publisher
  3. González Aguilera C, Tous C, Babiano R, de la Cruz J, Luna R, Aguilera A. Nab2 functions in the metabolism of RNA driven by polymerases II and III. Mol Biol Cell. 2011;22:2729-40 pubmed publisher
  4. Guo M, Xu F, Yamada J, Egelhofer T, Gao Y, Hartzog G, et al. Core structure of the yeast spt4-spt5 complex: a conserved module for regulation of transcription elongation. Structure. 2008;16:1649-58 pubmed publisher
    The Spt4-Spt5 complex is an essential RNA polymerase II elongation factor found in all eukaryotes and important for gene regulation. We report here the crystal structure of Saccharomyces cerevisiae Spt4 bound to the NGN domain of Spt5...
  5. Gaillard H, Tous C, Botet J, González Aguilera C, Quintero M, Viladevall L, et al. Genome-wide analysis of factors affecting transcription elongation and DNA repair: a new role for PAF and Ccr4-not in transcription-coupled repair. PLoS Genet. 2009;5:e1000364 pubmed publisher
  6. Quan T, Hartzog G. Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription. Genetics. 2010;184:321-34 pubmed publisher
    b>Spt4-Spt5, a general transcription elongation factor for RNA polymerase II, also has roles in chromatin regulation. However, the relationships between these functions are not clear...
  7. Ding B, Lejeune D, Li S. The C-terminal repeat domain of Spt5 plays an important role in suppression of Rad26-independent transcription coupled repair. J Biol Chem. 2010;285:5317-26 pubmed publisher
    ..Rad26, the yeast homolog of the human Cockayne syndrome group B (CSB) protein, plays an important role in TCR. Spt4, a transcription elongation factor that forms a complex with Spt5, has been shown to suppress TCR in rad26Delta ..
  8. Drouin S, Laramée L, Jacques P, Forest A, Bergeron M, Robert F. DSIF and RNA polymerase II CTD phosphorylation coordinate the recruitment of Rpd3S to actively transcribed genes. PLoS Genet. 2010;6:e1001173 pubmed publisher
    ..Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes...
  9. Xiao Y, Yang Y, Burckin T, Shiue L, Hartzog G, Segal M. Analysis of a splice array experiment elucidates roles of chromatin elongation factor Spt4-5 in splicing. PLoS Comput Biol. 2005;1:e39 pubmed
    ..of these linkages include Ceg1, a component of the mRNA capping enzyme, and the chromatin elongation factors Spt4-5, both of which have recently been shown to play a role in the normal splicing of several genes in the yeast ..

More Information


  1. Rondon A, Garcia Rubio M, González Barrera S, Aguilera A. Molecular evidence for a positive role of Spt4 in transcription elongation. EMBO J. 2003;22:612-20 pubmed
    ..Using a newly developed in vitro transcription elongation assay, we show that Spt4 is required in elongation...
  2. Murray S, Udupa R, Yao S, Hartzog G, Prelich G. Phosphorylation of the RNA polymerase II carboxy-terminal domain by the Bur1 cyclin-dependent kinase. Mol Cell Biol. 2001;21:4089-96 pubmed
    ..These results identify Bur1 as a fourth S. cerevisiae CTD kinase and provide striking functional similarities between Bur1 and metazoan P-TEFb. ..
  3. Jansen L, den Dulk H, Brouns R, de Ruijter M, Brandsma J, Brouwer J. Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair. EMBO J. 2000;19:6498-507 pubmed
    ..Using a genome-wide mutagenesis approach, we found that deletion of the SPT4 gene suppresses the rad26 defect...
  4. deSilva H, Lee K, Osley M. Functional dissection of yeast Hir1p, a WD repeat-containing transcriptional corepressor. Genetics. 1998;148:657-67 pubmed
    ..It was additionally found that the Hir1p WD repeats functionally interacted with the SPT4, SPT5, and SPT6 gene products, suggesting that these repeats may direct Hir1p to different protein complexes.
  5. Swanson M, Winston F. SPT4, SPT5 and SPT6 interactions: effects on transcription and viability in Saccharomyces cerevisiae. Genetics. 1992;132:325-36 pubmed
    The SPT4, SPT5 and SPT6 genes of Saccharomyces cerevisiae were identified originally by mutations that suppress delta insertion mutations at HIS4 and LYS2...
  6. Hartzog G, Wada T, Handa H, Winston F. Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev. 1998;12:357-69 pubmed
    Previous characterization of the Saccharomyces cerevisiae Spt4, Spt5, and Spt6 proteins suggested that these proteins act as transcription factors that modify chromatin structure...
  7. Shen Z, St Denis A, Chartrand P. Cotranscriptional recruitment of She2p by RNA pol II elongation factor Spt4-Spt5/DSIF promotes mRNA localization to the yeast bud. Genes Dev. 2010;24:1914-26 pubmed publisher
    ..She2p interacts in vivo with the elongating forms of RNA polymerase II (pol II) via the transcription elongation factor Spt4-Spt5...
  8. Schneider D, French S, Osheim Y, Bailey A, Vu L, Dodd J, et al. RNA polymerase II elongation factors Spt4p and Spt5p play roles in transcription elongation by RNA polymerase I and rRNA processing. Proc Natl Acad Sci U S A. 2006;103:12707-12 pubmed
    ..These data suggest that Spt4p, Spt5p, and, potentially, other regulators of Pol I transcription elongation play important roles in coupling rRNA transcription to its processing and ribosome assembly. ..
  9. Bucheli M, Buratowski S. Npl3 is an antagonist of mRNA 3' end formation by RNA polymerase II. EMBO J. 2005;24:2150-60 pubmed
    ..Mutations in elongation factors Spt4 and Spt6 suppress the readthrough phenotype, presumably by decreasing the amount of polymerase transcribing through ..
  10. Martinez Rucobo F, Sainsbury S, Cheung A, Cramer P. Architecture of the RNA polymerase-Spt4/5 complex and basis of universal transcription processivity. EMBO J. 2011;30:1302-10 pubmed publisher
    ..Spt5 associates with Spt4 to form the Spt4/5 heterodimer...
  11. Lindstrom D, Hartzog G. Genetic interactions of Spt4-Spt5 and TFIIS with the RNA polymerase II CTD and CTD modifying enzymes in Saccharomyces cerevisiae. Genetics. 2001;159:487-97 pubmed
    ..We investigated relationships between three classes of these factors: (1) transcription elongation factors Spt4-Spt5, TFIIS, and Spt16; (2) the C-terminal heptapeptide repeat domain (CTD) of RNA polymerase II; and (3) protein ..
  12. Basrai M, Kingsbury J, Koshland D, Spencer F, Hieter P. Faithful chromosome transmission requires Spt4p, a putative regulator of chromatin structure in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16:2838-47 pubmed
    ..The gene complementing the s138 mutation was found to be identical to the S. cerevisiae SPT4 gene...
  13. Laribee R, Krogan N, Xiao T, Shibata Y, Hughes T, Greenblatt J, et al. BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex. Curr Biol. 2005;15:1487-93 pubmed
    ..Our data reveal a novel function for the BUR kinase in transcriptional regulation through the selective control of histone modifications. ..
  14. Costa P, Arndt K. Synthetic lethal interactions suggest a role for the Saccharomyces cerevisiae Rtf1 protein in transcription elongation. Genetics. 2000;156:535-47 pubmed
    ..of this view, we show that RTF1 functionally interacts with genes that encode known elongation factors, including SPT4, SPT5, SPT16, and PPR2...
  15. Formosa T, Eriksson P, Wittmeyer J, Ginn J, Yu Y, Stillman D. Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucleosome-binding factor SPN. EMBO J. 2001;20:3506-17 pubmed
    ..These complexes have altered electrophoretic mobility and a distinct pattern of enhanced sensitivity to DNase I. These results suggest that Spt16-Pob3 and Nhp6 cooperate to function as a novel nucleosome reorganizing factor. ..
  16. Crickard J, Fu J, Reese J. 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. J Biol Chem. 2016;291:9853-70 pubmed publisher
    ..between NusG/Spt5 and RNA polymerase in prokaryotes, little is known about how the binding of eukaryotic Spt4/5 affects the biochemical activities of RNAPII...
  17. McKay S, Johnson T. An investigation of a role for U2 snRNP spliceosomal components in regulating transcription. PLoS ONE. 2011;6:e16077 pubmed publisher
  18. Cui P, Jin H, Vutukuru M, Kaplan C. Relationships Between RNA Polymerase II Activity and Spt Elongation Factors to Spt- Phenotype and Growth in Saccharomyces cerevisiae. G3 (Bethesda). 2016;6:2489-504 pubmed publisher
    ..both cooperating and antagonistic genetic interactions between Pol II alleles and alleles of elongation factors SPT4, SPT5, and SPT6 We find that cryptic transcription at FLO8 and STE11 is distinct from that at lys2-128?, though all ..
  19. Zhang L, Fletcher A, Cheung V, Winston F, Stargell L. Spn1 regulates the recruitment of Spt6 and the Swi/Snf complex during transcriptional activation by RNA polymerase II. Mol Cell Biol. 2008;28:1393-403 pubmed
    ..These findings link Spn1 functions to the transition from an inactive to an actively transcribing RNAPII complex at a postrecruitment-regulated promoter. ..
  20. Leporé N, Lafontaine D. A functional interface at the rDNA connects rRNA synthesis, pre-rRNA processing and nucleolar surveillance in budding yeast. PLoS ONE. 2011;6:e24962 pubmed publisher
    ..Both the Spt4-Spt5, and the Nrd1-Nab3 complexes interact functionally with Rrp6, and colocalize at the rDNA...
  21. Liu C, Chang C, Chern Y, Wang T, Hsieh W, Shen W, et al. Spt4 is selectively required for transcription of extended trinucleotide repeats. Cell. 2012;148:690-701 pubmed publisher
    ..cerevisiae, we discovered that transcription elongation factor Spt4 is required to transcribe long trinucleotide repeats located either in ORFs or nonprotein-coding ..
  22. Smith Kinnaman W, Berna M, Hunter G, True J, Hsu P, Cabello G, et al. The interactome of the atypical phosphatase Rtr1 in Saccharomyces cerevisiae. Mol Biosyst. 2014;10:1730-41 pubmed publisher
    ..Interestingly, we found that the interaction between Rtr1 and RNAPII is decreased in ctk1? strains. We hypothesize that serine-2 CTD phosphorylation is required for Rtr1 recruitment to RNAPII during transcription elongation. ..
  23. Silva A, Cavero S, Begley V, Sole C, Böttcher R, Chávez S, et al. Regulation of transcription elongation in response to osmostress. PLoS Genet. 2017;13:e1007090 pubmed publisher
    ..Hog1 phosphorylates the Spt4 elongation factor at Thr42 and Ser43 and such phosphorylations are essential for the overall transcriptional ..
  24. Ubukata T, Shimizu T, Adachi N, Sekimizu K, Nakanishi T. Cleavage, but not read-through, stimulation activity is responsible for three biologic functions of transcription elongation factor S-II. J Biol Chem. 2003;278:8580-5 pubmed
    ..Furthermore, strains having a genotype consisting of one of these S-II mutations and the spt4 null mutation grew as well as the spt4 null mutant at 37 degrees C, a restrictive temperature for a strain bearing ..
  25. Reyes Reyes M, Hampsey M. Role for the Ssu72 C-terminal domain phosphatase in RNA polymerase II transcription elongation. Mol Cell Biol. 2007;27:926-36 pubmed
    ..Furthermore, deletion of SPT4, which encodes a subunit of the Spt4-Spt5 early elongation complex, also suppresses ssu72-2, whereas the spt5-242 ..
  26. McCullock S, Kinard T, McCullough L, Formosa T. blm3-1 is an allele of UBP3, a ubiquitin protease that appears to act during transcription of damaged DNA. J Mol Biol. 2006;363:660-72 pubmed
  27. Chen Y, Baker R, Keith K, Harris K, Stoler S, Fitzgerald Hayes M. The N terminus of the centromere H3-like protein Cse4p performs an essential function distinct from that of the histone fold domain. Mol Cell Biol. 2000;20:7037-48 pubmed
    ..The structure-function characteristics of the Cse4p N terminus are relevant to understanding how other H3-like proteins, such as the human homolog CENP-A, function in kinetochore assembly and chromosome segregation. ..
  28. Howard S, Hester A, Herman P. The Ras/PKA signaling pathway may control RNA polymerase II elongation via the Spt4p/Spt5p complex in Saccharomyces cerevisiae. Genetics. 2003;165:1059-70 pubmed
    ..First, the growth of spt4 and spt5 mutants was found to be very sensitive to changes in Ras/PKA signaling activity...
  29. Chen X, Ding B, Lejeune D, Ruggiero C, Li S. Rpb1 sumoylation in response to UV radiation or transcriptional impairment in yeast. PLoS ONE. 2009;4:e5267 pubmed publisher
    ..Our results demonstrate a novel covalent modification of Rpb1 in response to UV induced DNA damage or transcriptional impairment, and unravel an important link between the modification and the DNA damage checkpoint response. ..
  30. Gomar Alba M, del Olmo M. Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes. Biochem J. 2016;473:3065-79 pubmed publisher
    ..and posttranscriptional processes: for example, transcription co-activator Sub1 and elongation complex Spt4/5...
  31. Kvint K, Uhler J, Taschner M, Sigurdsson S, Erdjument Bromage H, Tempst P, et al. Reversal of RNA polymerase II ubiquitylation by the ubiquitin protease Ubp3. Mol Cell. 2008;30:498-506 pubmed publisher
    ..In agreement with this, cells with compromised DNA repair are better equipped to survive UV damage when UPB3 is deleted. ..
  32. Garcia A, Collin A, Calvo O. Sub1 associates with Spt5 and influences RNA polymerase II transcription elongation rate. Mol Biol Cell. 2012;23:4297-312 pubmed publisher
    ..Taken together, our results indicate that Sub1 associates with Spt5 and influences Spt5-Rpb1 complex levels and consequently transcription elongation rate. ..
  33. Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J, et al. A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2006;439:497-501 pubmed
    ..The dephosphorylation of gammaH2AX by the HTP-C is necessary for efficient recovery from the DNA damage checkpoint. ..
  34. Anderson S, Sikes M, Zhang Y, French S, Salgia S, Beyer A, et al. The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. J Biol Chem. 2011;286:18816-24 pubmed publisher
    ..Pol) I; however, previous studies only characterized defects in Pol I transcription induced by deletion of SPT4. Here we describe two new, partially active mutations in SPT5 and use these mutant strains to characterize the ..
  35. Prather D, Krogan N, Emili A, Greenblatt J, Winston F. Identification and characterization of Elf1, a conserved transcription elongation factor in Saccharomyces cerevisiae. Mol Cell Biol. 2005;25:10122-35 pubmed
    ..lethality between an elf1Delta mutation and mutations in genes encoding several known elongation factors, including Spt4, Spt5, Spt6, and members of the Paf1 complex...
  36. Blythe A, Gunasekara S, Walshe J, Mackay J, Hartzog G, Vrielink A. Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5. Protein Expr Purif. 2014;100:54-60 pubmed publisher
    b>Spt4/5 is a hetero-dimeric transcription elongation factor that can both inhibit and promote transcription elongation by RNA polymerase II (RNAPII). However, Spt4/5's mechanism of action remains elusive...
  37. Li W, Selvam K, Rahman S, Li S. Sen1, the yeast homolog of human senataxin, plays a more direct role than Rad26 in transcription coupled DNA repair. Nucleic Acids Res. 2016;44:6794-802 pubmed publisher
    ..Unlike Rad26, which becomes completely dispensable for TCR in cells lacking the TCR repressor Spt4, Sen1 is still required for efficient TCR in the absence of Spt4...
  38. Blythe A, Yazar Klosinski B, Webster M, Chen E, Vandevenne M, Bendak K, et al. The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein. Protein Sci. 2016;25:1710-21 pubmed publisher
    The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co-transcriptional pre-mRNA processing; however, the mechanisms by which Spt4/5 acts are ..
  39. Gómez Navarro N, Peiró Chova L, Estruch F. Iwr1 facilitates RNA polymerase II dynamics during transcription elongation. Biochim Biophys Acta Gene Regul Mech. 2017;1860:803-811 pubmed publisher
    ..Moreover, absence of Iwr1 causes genome instability that is enhanced by defects in the DNA repair machinery. ..
  40. Gibney P, Fries T, Bailer S, Morano K. Rtr1 is the Saccharomyces cerevisiae homolog of a novel family of RNA polymerase II-binding proteins. Eukaryot Cell. 2008;7:938-48 pubmed publisher
    ..Taken together, our data reveal a role for members of the RTR1/RPAP2 family as regulators of core RNAPII function. ..
  41. Morillon A, Karabetsou N, O Sullivan J, Kent N, Proudfoot N, Mellor J. Isw1 chromatin remodeling ATPase coordinates transcription elongation and termination by RNA polymerase II. Cell. 2003;115:425-35 pubmed
    ..Overall these studies establish the central role played by Isw1p in the coordination of transcription. ..
  42. Crickard J, Lee J, Lee T, Reese J. The elongation factor Spt4/5 regulates RNA polymerase II transcription through the nucleosome. Nucleic Acids Res. 2017;45:6362-6374 pubmed publisher
    ..However, RNAPII is decorated with elongation factors as it transcribes the genome. One such factor, Spt4/5, becomes an integral component of the elongation complex, making direct contact with the 'jaws' of RNAPII and ..
  43. Stevens J, O Donnell A, Perry T, Benjamin J, Barnes C, Johnston G, et al. FACT, the Bur kinase pathway, and the histone co-repressor HirC have overlapping nucleosome-related roles in yeast transcription elongation. PLoS ONE. 2011;6:e25644 pubmed publisher
    ..used to show that certain Spt16 activities collaborate with histone acetylation and the activities of a Bur-kinase/Spt4-Spt5/Paf1C pathway that facilitate transcription elongation...
  44. Wu X, Rossettini A, Hanes S. The ESS1 prolyl isomerase and its suppressor BYE1 interact with RNA pol II to inhibit transcription elongation in Saccharomyces cerevisiae. Genetics. 2003;165:1687-702 pubmed
    ..This led to the finding that Ess1 also inhibits elongation; Ess1 opposes elongation factors Dst1 and Spt4/5, and overexpression of ESS1 makes cells more sensitive to the elongation inhibitor 6-AU...
  45. Crotti L, Basrai M. Functional roles for evolutionarily conserved Spt4p at centromeres and heterochromatin in Saccharomyces cerevisiae. EMBO J. 2004;23:1804-14 pubmed
    ..We established that evolutionarily conserved Saccharomyces cerevisiae SPT4, previously identified in genetic screens for defects in chromosome transmission fidelity (ctf), encodes a new ..
  46. Deshpande S, Sadhale P, Vijayraghavan U. Involvement of S. cerevisiae Rpb4 in subset of pathways related to transcription elongation. Gene. 2014;545:126-31 pubmed publisher
    ..Yet we find strong genetic interaction of rpb4? with mutants in many transcription elongation factors such as Paf1, Spt4, Dst1, Elp3 and Rpb9...
  47. Compagnone Post P, Osley M. Mutations in the SPT4, SPT5, and SPT6 genes alter transcription of a subset of histone genes in Saccharomyces cerevisiae. Genetics. 1996;143:1543-54 pubmed
    The SPT4, SPT5, and SPT6 gene products define a class of transcriptional repressors in Saccharomyces cerevisiae that are thought to function through their effects on chromatin assembly or stability...
  48. Santisteban M, Hang M, Smith M. Histone variant H2A.Z and RNA polymerase II transcription elongation. Mol Cell Biol. 2011;31:1848-60 pubmed publisher
  49. Proft M, Mas G, de Nadal E, Vendrell A, Noriega N, Struhl K, et al. The stress-activated Hog1 kinase is a selective transcriptional elongation factor for genes responding to osmotic stress. Mol Cell. 2006;23:241-50 pubmed
    ..Thus, in addition to its various functions during transcriptional initiation, Hog1 behaves as a transcriptional elongation factor that is selective for genes induced upon osmotic stress. ..
  50. Wolffe A, Pruss D. Hanging on to histones. Chromatin. Curr Biol. 1996;6:234-7 pubmed
  51. Mayekar M, Gardner R, Arndt K. The recruitment of the Saccharomyces cerevisiae Paf1 complex to active genes requires a domain of Rtf1 that directly interacts with the Spt4-Spt5 complex. Mol Cell Biol. 2013;33:3259-73 pubmed publisher
    ..Collectively, our results provide molecular insight into a key attachment point between Paf1C and the RNA polymerase II elongation machinery...
  52. Bennett C, Westmoreland T, Verrier C, Blanchette C, Sabin T, Phatnani H, et al. Yeast screens identify the RNA polymerase II CTD and SPT5 as relevant targets of BRCA1 interaction. PLoS ONE. 2008;3:e1448 pubmed publisher
    ..These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1) to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, ..
  53. Gómez Herreros F, Margaritis T, Rodríguez Galán O, Pelechano V, Begley V, Millán Zambrano G, et al. The ribosome assembly gene network is controlled by the feedback regulation of transcription elongation. Nucleic Acids Res. 2017;45:9302-9318 pubmed publisher
    ..On the whole, this work uncovers a feedback control of ribosome biogenesis by fine-tuning transcription elongation in ribosome assembly factor-coding genes. ..