DSIF

File:RNA polymerase II elongation control.jpg

DSIF (DRB Sensitivity Inducing Factor) is a protein complex that can either negatively or positively affect transcription by RNA polymerase II (Pol II).{{cite journal | vauthors = Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, Sugimoto S, Yano K, Hartzog GA, Winston F, Buratowski S, Handa H | display-authors = 6 | title = DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs | journal = Genes & Development | volume = 12 | issue = 3 | pages = 343–356 | date = February 1998 | pmid = 9450929 | pmc = 316480 | doi = 10.1101/gad.12.3.343 }} It can interact with the negative elongation factor (NELF) to promote the stalling of Pol II at some genes, which is called promoter proximal pausing.{{Cite journal |last1=Tettey |first1=Theophilus T. |last2=Gao |first2=Xin |last3=Shao |first3=Wanqing |last4=Li |first4=Hua |last5=Story |first5=Benjamin A. |last6=Chitsazan |first6=Alex D. |last7=Glaser |first7=Robert L. |last8=Goode |first8=Zach H. |last9=Seidel |first9=Christopher W. |last10=Conaway |first10=Ronald C. |last11=Zeitlinger |first11=Julia |last12=Blanchette |first12=Marco |last13=Conaway |first13=Joan W. |date=2019-06-25 |title=A Role for FACT in RNA Polymerase II Promoter-Proximal Pausing |journal=Cell Reports |language=en |volume=27 |issue=13 |pages=3770–3779.e7 |doi=10.1016/j.celrep.2019.05.099|doi-access=free |pmid=31242411 }} The pause occurs soon after initiation, once 20–60 nucleotides have been transcribed. This stalling is relieved by positive transcription elongation factor b (P-TEFb) and Pol II enters productive elongation to resume synthesis till finish. In humans, DSIF is composed of hSPT4 and hSPT5. hSPT5 has a direct role in mRNA capping which occurs while the elongation is paused. {{Cite journal |last1=Wen |first1=Y. |last2=Shatkin |first2=A. J. |date=1999-07-15 |title=Transcription elongation factor hSPT5 stimulates mRNA capping |journal=Genes & Development |language=en |volume=13 |issue=14 |pages=1774–1779 |doi=10.1101/gad.13.14.1774 |issn=0890-9369|doi-access=free |pmid=10421630 |pmc=316881 }}

SPT5 is preserved in humans to bacteria.{{Cite journal |last=Decker |first=Tim-Michael |date=2021-07-09 |title=Mechanisms of Transcription Elongation Factor DSIF (Spt4–Spt5) |url=https://linkinghub.elsevier.com/retrieve/pii/S0022283620305581 |journal=Journal of Molecular Biology |language=en |volume=433 |issue=14 |pages=166657 |doi=10.1016/j.jmb.2020.09.016|pmid=32987031 |url-access=subscription }} SPT4 and SPT5 in yeast are the homologs of hSPT4 and hSPT5.{{Cite journal |last1=Wenzel |first1=Sabine |last2=Schweimer |first2=Kristian |last3=Rösch |first3=Paul |last4=Wöhrl |first4=Birgitta M. |date=2008-06-06 |title=The small hSpt4 subunit of the human transcription elongation factor DSIF is a Zn-finger protein with α/β type topology |url=https://linkinghub.elsevier.com/retrieve/pii/S0006291X08005640 |journal=Biochemical and Biophysical Research Communications |language=en |volume=370 |issue=3 |pages=414–418 |doi=10.1016/j.bbrc.2008.03.080|pmid=18373978 |url-access=subscription }} In bacteria, the homologous complex only contains NusG, a Spt5 homolog.{{Cite journal |last1=Yakhnin |first1=Alexander V. |last2=Murakami |first2=Katsuhiko S. |last3=Babitzke |first3=Paul |date=2016-03-04 |title=NusG Is a Sequence-specific RNA Polymerase Pause Factor That Binds to the Non-template DNA within the Paused Transcription Bubble |journal=Journal of Biological Chemistry |language=en |volume=291 |issue=10 |pages=5299–5308 |doi=10.1074/jbc.M115.704189|doi-access=free |pmid=26742846 |pmc=4777861 }} Archaea have both proteins.{{cite journal | vauthors = Fouqueau T, Blombach F, Cackett G, Carty AE, Matelska DM, Ofer S, Pilotto S, Phung DK, Werner F | display-authors = 6 | title = The cutting edge of archaeal transcription | journal = Emerging Topics in Life Sciences | volume = 2 | issue = 4 | pages = 517–533 | date = December 2018 | pmid = 33525828 | pmc = 7289017 | doi = 10.1042/ETLS20180014 | doi-access = free }}

The complex locks the RNA polymerase (RNAP) clamp into a closed state to prevent the elongation complex (EC) from dissociating. The Spt5 NGN domain helps anneal the two strands of DNA upstream. The single KOW domain in bacteria and archaea anchors a ribosome to the RNAP.