DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs

Tadashi Wada, Toshiyuki Takagi, Yuki Yamaguchi, Anwarul Ferdous, Takeshi Imai, Susumu Hirose, Seiji Sugimoto, Keiichi Yano, Grant A. Hartzog, Fred Winston, Stephen Buratowski, Hiroshi Handa

Research output: Contribution to journalArticle

477 Citations (Scopus)

Abstract

We report the identification of a transcription elongation factor from HeLa cell nuclear extracts that causes pausing of RNA polymerase II (Pol II) in conjunction with the transcription inhibitor 5,6-dichloro-1-β-D- ribofuranosylbenzimidazole (DRB). This factor, termed DRB sensitivity- inducing factor (DSIF), is also required for transcription inhibition by H8. DSIF has been purified and is composed of 160-kD (p160) and 14-kD (p14) subunits. Isolation of a cDNA encoding DSIF p160 shows it to be a homolog of the Saccharomyces cerevisiae transcription factor Spt5. Recombinant Supt4h protein, the human homolog of yeast Spt4, is functionally equivalent to DSIF p14, indicating that DSIF is composed of the human homologs of Spt4 and Spt5. In addition to its negative role in elongation, DSIF is able to stimulate the rate of elongation by RNA Pol II in a reaction containing limiting concentrations of ribonucleoside triphosphates. A role for DSIF in transcription elongation is further supported by the fact that p160 has a region homologous to the bacterial elongation factor NusG. The combination of biochemical studies on DSIF and genetic analysis of Spt4 and Spt5 in yeast, also in this issue, indicates that DSIF associates with RNA Pol II and regulates its processivity in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)343-356
Number of pages14
JournalGenes and Development
Volume12
Issue number3
StatePublished - Feb 1 1998

Fingerprint

Dichlororibofuranosylbenzimidazole
Peptide Elongation Factors
RNA Polymerase II
Transcription Factors
Yeasts
Ribonucleosides
Cell Extracts
HeLa Cells
Recombinant Proteins
Statistical Factor Analysis
Saccharomyces cerevisiae
Complementary DNA

Keywords

  • DRB
  • DSIF
  • NusG
  • Protein phosphorylation
  • Transcription elongation
  • Transcription elongation factor
  • Transcription inhibitor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. / Wada, Tadashi; Takagi, Toshiyuki; Yamaguchi, Yuki; Ferdous, Anwarul; Imai, Takeshi; Hirose, Susumu; Sugimoto, Seiji; Yano, Keiichi; Hartzog, Grant A.; Winston, Fred; Buratowski, Stephen; Handa, Hiroshi.

In: Genes and Development, Vol. 12, No. 3, 01.02.1998, p. 343-356.

Research output: Contribution to journalArticle

Wada, T, Takagi, T, Yamaguchi, Y, Ferdous, A, Imai, T, Hirose, S, Sugimoto, S, Yano, K, Hartzog, GA, Winston, F, Buratowski, S & Handa, H 1998, 'DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs', Genes and Development, vol. 12, no. 3, pp. 343-356.
Wada, Tadashi ; Takagi, Toshiyuki ; Yamaguchi, Yuki ; Ferdous, Anwarul ; Imai, Takeshi ; Hirose, Susumu ; Sugimoto, Seiji ; Yano, Keiichi ; Hartzog, Grant A. ; Winston, Fred ; Buratowski, Stephen ; Handa, Hiroshi. / DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. In: Genes and Development. 1998 ; Vol. 12, No. 3. pp. 343-356.
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abstract = "We report the identification of a transcription elongation factor from HeLa cell nuclear extracts that causes pausing of RNA polymerase II (Pol II) in conjunction with the transcription inhibitor 5,6-dichloro-1-β-D- ribofuranosylbenzimidazole (DRB). This factor, termed DRB sensitivity- inducing factor (DSIF), is also required for transcription inhibition by H8. DSIF has been purified and is composed of 160-kD (p160) and 14-kD (p14) subunits. Isolation of a cDNA encoding DSIF p160 shows it to be a homolog of the Saccharomyces cerevisiae transcription factor Spt5. Recombinant Supt4h protein, the human homolog of yeast Spt4, is functionally equivalent to DSIF p14, indicating that DSIF is composed of the human homologs of Spt4 and Spt5. In addition to its negative role in elongation, DSIF is able to stimulate the rate of elongation by RNA Pol II in a reaction containing limiting concentrations of ribonucleoside triphosphates. A role for DSIF in transcription elongation is further supported by the fact that p160 has a region homologous to the bacterial elongation factor NusG. The combination of biochemical studies on DSIF and genetic analysis of Spt4 and Spt5 in yeast, also in this issue, indicates that DSIF associates with RNA Pol II and regulates its processivity in vitro and in vivo.",
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