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DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs
Open accessAbstract
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-beta-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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“Phosphorylation of Ser5 of the Pol II CTD by transcription factor IIH (TFIIH) is required for transcription initiation, whereas phosphorylation of Ser2 of the Pol II CTD, of DSIF (DRB sensitivity inducing factor) and of NELF (negative elongation factor) by pTEFb (positive transcription elongation factor) is needed for transcription elongation141–143.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [141]
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Transcription elongation factor P-TEFb is required for HIV-1 Tat transactivation in vitroPreprint
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Metadata
- Authors
- Wada, T., Takagi, T., Yamaguchi, Y., Ferdous, A., Imai, T., Hirose, S., Sugimoto, S., Yano, K., Hartzog, G. A., Winston, F., Buratowski, S., & Handa, H.
- Affiliations
- National Institute of Genetics (JP)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-02-01
- Volume
- 12
- Issue
- 3
- Pages
- 343-356
- ISSN
- 0890-9369 (ISSN-L)
- PMC
- PMC316480
- OpenAlex
- W2148917483
- Cited by
- 750
- References
- 77
- Citations by year
- 2026: 23 · 2025: 18 · 2024: 33 · 2023: 20 · 2022: 24 · 2021: 38 · 2020: 32 · 2019: 24 · 2018: 24 · 2017: 21 · 2016: 28 · 2015: 24 · 2014: 23 · 2013: 31 · 2012: 28
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM032967, R37GM032967, GM 32967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- DSIF, transcription elongation, RNA polymerase II, processivity, Spt4, Spt5, transcriptional pausing, HeLa cells, Saccharomyces cerevisiae, cDNA cloning
- MeSH terms
- Amino Acid Sequence, Chromosomal Proteins, Non-Histone, Dichlororibofuranosylbenzimidazole, Fungal Proteins, HeLa Cells, Humans, Molecular Sequence Data, Nuclear Proteins, RNA Polymerase II, Saccharomyces cerevisiae, Sensitivity and Specificity, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Sequence Homology, Amino Acid, Nucleic Acid Synthesis Inhibitors, Saccharomyces cerevisiae Proteins, Transcriptional Elongation Factors
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