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DSIF (DRB Sensitivity Inducing Factor) is a protein complex that can either negatively or positively affect transcription by RNA polymerase II (Pol II).[2] It can interact with the negative elongation factor (NELF) to promote the stalling of Pol II which is called promoter proximal pausing.[3] The pause occurs soon after initiation, once 20-60 nucleotides have been transcribed.[3] This stalling is relieved by positive transcription elongation factor b (P-TEFb) and Pol II enters productive elongation to resume synthesis till finish.[1] In humans, DSIF is composed of hSPT4 and hSPT5.[2] hSPT5 has a direct role in mRNA capping which occurs while the elongation is paused.[4]
SPT5 is preserved in humans to bacteria.[5] SPT4 and SPT5 in yeast are the homologs of hSPT4 and hSPT5.[2] In bacteria, the homologous complex only contains NusG, a Spt5 homolog.[6] Archaea have both proteins.[7]
DSIF plays the same role for HIV-1 gene expression as it would normally in transcription.[8][9] This is because P-TEFb phosphorylates DSIF the same regardless of whether or not P-TEFb goes through normal cellular regulation or bypasses it due to Tat. [10]
References
edit- ^ a b Zhou, Qiang; Li, Tiandao; Price, David H. (2012-07-07). "RNA Polymerase II Elongation Control". Annual Review of Biochemistry. 81 (1): 119–143. doi:10.1146/annurev-biochem-052610-095910. ISSN 0066-4154. PMC 4273853. PMID 22404626.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b c 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. (1998-02-01). "DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs". Genes & Development. 12 (3): 343–356. doi:10.1101/gad.12.3.343. ISSN 0890-9369.
- ^ a b Tettey, Theophilus T.; Gao, Xin; Shao, Wanqing; Li, Hua; Story, Benjamin A.; Chitsazan, Alex D.; Glaser, Robert L.; Goode, Zach H.; Seidel, Christopher W.; Conaway, Ronald C.; Zeitlinger, Julia; Blanchette, Marco; Conaway, Joan W. (2019-06-25). "A Role for FACT in RNA Polymerase II Promoter-Proximal Pausing". Cell Reports. 27 (13): 3770–3779.e7. doi:10.1016/j.celrep.2019.05.099. ISSN 2211-1247.
- ^ Wen, Yingxia; Shatkin, Aaron J. (1999-07-15). "Transcription elongation factor hSPT5 stimulates mRNA capping". Genes & Development. 13 (14): 1774–1779. doi:10.1101/gad.13.14.1774. ISSN 0890-9369. PMC 316881. PMID 10421630.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Decker, Tim-Michael (2021-07-09). "Mechanisms of Transcription Elongation Factor DSIF (Spt4–Spt5)". Journal of Molecular Biology. RNA polymerase II Transcription. 433 (14): 166657. doi:10.1016/j.jmb.2020.09.016. ISSN 0022-2836.
- ^ Yakhnin, Alexander V.; Murakami, Katsuhiko S.; Babitzke, Paul (2016-03-04). "NusG Is a Sequence-specific RNA Polymerase Pause Factor That Binds to the Non-template DNA within the Paused Transcription Bubble*". Journal of Biological Chemistry. 291 (10): 5299–5308. doi:10.1074/jbc.M115.704189. ISSN 0021-9258.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Sanders, Travis J.; Lammers, Marshall; Marshall, Craig J.; Walker, Julie E.; Lynch, Erin R.; Santangelo, Thomas J. (2018-12-27). "TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin". Molecular Microbiology. 111 (3): 784–797. doi:10.1111/mmi.14191. ISSN 0950-382X. PMC 6417941. PMID 30592095.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Zhang, Zhiqiang; Klatt, Alicia; Gilmour, David S.; Henderson, Andrew J. (2007-06-08). "Negative Elongation Factor NELF Represses Human Immunodeficiency Virus Transcription by Pausing the RNA Polymerase II Complex". Journal of Biological Chemistry. 282 (23): 16981–16988. doi:10.1074/jbc.m610688200. ISSN 0021-9258.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Ping, Yueh-Hsin; Rana, Tariq M. (2001-04-20). "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". Journal of Biological Chemistry. 276 (16): 12951–12958. doi:10.1074/jbc.m006130200. ISSN 0021-9258.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Zhu, Yuerong; Pe’ery, Tsafrira; Peng, Junmin; Ramanathan, Yegnanarayana; Marshall, Nick; Marshall, Tricia; Amendt, Brad; Mathews, Michael B.; Price, David H. (1997-10-15). "Transcription elongation factor P-TEFb is required for HIV-1 Tat transactivation in vitro". Genes & Development. 11 (20): 2622–2632. doi:10.1101/gad.11.20.2622. ISSN 0890-9369. PMC 316609. PMID 9334325.
{{cite journal}}: CS1 maint: PMC format (link)
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