View source for Transcription preinitiation complex

{{short description|Complex of proteins necessary for gene transcription in eukaryotes and archaea}}
[[File:Figure 16 04 01.jpg|alt=Cluster of ovals representing the transcription preinitiation complex is sandwiched inside a curved strand of DNA, between the promoter region on one end and the enhancer region on the other.|thumb|Transcription preinitiation complex, represented by the central cluster of proteins, causes RNA polymerase to bind to target DNA site. The PIC is able to bind both the promoter sequence near the gene to be transcribed and an enhancer sequence in a different part of the genome, allowing enhancer sequences to regulate a gene distant from it.]]
The '''preinitiation complex''' (abbreviated '''PIC''') is a complex of approximately 100 [[protein]]s that is necessary for the [[transcription (genetics)|transcription]] of protein-coding [[gene]]s in [[eukaryote]]s and [[archaea]].  The preinitiation complex positions [[RNA polymerase II]] (Pol II) at gene [[transcription start site]]s, [[DNA melting|denatures]] the [[DNA]], and positions the DNA in the RNA polymerase II [[active site]] for transcription.<ref name="pmid11092823">{{cite journal | vauthors = Lee TI, Young RA | title = Transcription of eukaryotic protein-coding genes | journal = Annual Review of Genetics | volume = 34 | pages = 77–137 | year = 2000 | pmid = 11092823 | doi = 10.1146/annurev.genet.34.1.77 }}</ref><ref name="pmid17670940">{{cite journal | vauthors = Kornberg RD | title = The molecular basis of eukaryotic transcription | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 32 | pages = 12955–61 | date = August 2007 | pmid = 17670940 | pmc = 1941834 | doi = 10.1073/pnas.0704138104 | author-link = Roger D. Kornberg | bibcode = 2007PNAS..10412955K | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kim TK, Lagrange T, Wang YH, Griffith JD, Reinberg D, Ebright RH | title = Trajectory of DNA in the RNA polymerase II transcription preinitiation complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 23 | pages = 12268–73 | date = November 1997 | pmid = 9356438 | pmc = 24903 | doi = 10.1073/pnas.94.23.12268 | author6-link = Richard H. Ebright | bibcode = 1997PNAS...9412268K | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kim TK, Ebright RH, Reinberg D | title = Mechanism of ATP-dependent promoter melting by transcription factor IIH | journal = Science | volume = 288 | issue = 5470 | pages = 1418–22 | date = May 2000 | pmid = 10827951 | doi = 10.1126/science.288.5470.1418 | author2-link = Richard H. Ebright | bibcode = 2000Sci...288.1418K }}</ref>

The minimal PIC includes RNA polymerase II and six [[general transcription factor]]s: [[Transcription factor II A|TF<sub>II</sub>A]], [[Transcription factor II B|TF<sub>II</sub>B]], [[Transcription factor II D|TF<sub>II</sub>D]], [[Transcription factor II E|TF<sub>II</sub>E]], [[Transcription factor II F|TF<sub>II</sub>F]], and [[Transcription factor II H|TF<sub>II</sub>H]]. Additional regulatory complexes (such as the [[mediator (coactivator)|mediator]] coactivator<ref name="Allen_2015">{{cite journal | vauthors = Allen BL, Taatjes DJ | title = The Mediator complex: a central integrator of transcription | journal = Nature Reviews. Molecular Cell Biology | volume = 16 | issue = 3 | pages = 155–66 | year = 2015 | pmid = 25693131 | pmc = 4963239 | doi = 10.1038/nrm3951 }}</ref> and [[chromatin structure remodeling (RSC) complex|chromatin remodeling]] complexes) may also be components of the PIC.

Preinitiation complexes are also formed during RNA Polymerase I and RNA Polymerase III transcription.

==Assembly (RNA Polymerase II)==
{{Unreferenced section|date=April 2019}}
{{main|RNA polymerase II holoenzyme#Assembly of the PIC}}

A classical view of PIC formation at the promoter involves the following steps:

* [[TATA binding protein]] (TBP, a subunit of TFIID) binds the [[promoter (genetics)|promoter]], creating a sharp bend in the promoter DNA.<ref>{{Cite journal |last1=Ossipow |first1=Vincent |last2=Fonjallaz |first2=Philippe |last3=Schibler |first3=Ueli |date=1999-02-01 |title=An RNA Polymerase II Complex Containing All Essential Initiation Factors Binds to the Activation Domain of PAR Leucine Zipper Transcription Factor Thyroid Embryonic Factor |journal=Molecular and Cellular Biology |language=en |volume=19 |issue=2 |pages=1242–1250 |doi=10.1128/MCB.19.2.1242 |issn=1098-5549 |pmc=116053 |pmid=9891058}}</ref>
** Animals have some TBP-related factors (TRF; [[TBPL1]]/[[TBPL2]]). They can replace TBP in some special contexts.<ref name=pmid25661246>{{cite journal |last1=Duttke |first1=SH |title=Evolution and diversification of the basal transcription machinery. |journal=Trends in Biochemical Sciences |date=March 2015 |volume=40 |issue=3 |pages=127–9 |doi=10.1016/j.tibs.2015.01.005 |pmid=25661246 |pmc=4410091}}</ref>
* TBP recruits TFIIA, then TFIIB, to the promoter.
* TFIIB recruits RNA polymerase II and TFIIF to the promoter.
* TFIIE joins the growing complex and recruits TFIIH which has protein kinase activity (phosphorylates RNA polymerase II within the CTD) and DNA helicase activity (unwinds DNA at promoter). It also recruits nucleotide-excision repair proteins.
* Subunits within TFIIH that have [[ATPase]] and [[helicase]] activity create negative [[DNA supercoil|superhelical]] tension in the DNA.
* Negative superhelical tension causes approximately one turn of DNA to [[DNA melting|unwind]] and form the [[transcription bubble]].  
* The template strand of the transcription bubble engages with the RNA polymerase II active site.
* RNA synthesis begins.
* After synthesis of ~10 nucleotides of RNA, and an obligatory phase of several abortive transcription cycles, RNA polymerase II escapes the promoter region to transcribe the remainder of the gene.

An alternative hypothesis of PIC assembly postulates the recruitment of a pre-assembled "[[RNA polymerase II holoenzyme]]" directly to the promoter (composed of all, or nearly all GTFs and RNA polymerase II and regulatory complexes), in a manner similar to the bacterial RNA polymerase (RNAP).

== Other preinitiation complexes ==

=== In Archaea ===
Archaea have a preinitiation complex resembling that of a minimized Pol II PIC, with a TBP and an [[Archaeal transcription factor B]] (TFB, a TFIIB homolog). The assembly follows a similar sequence, starting with TBP binding to the promoter. An interesting aspect is that the entire complex is bound in an inverse orientation compared to those found in eukaryotic PIC.<ref>{{cite journal |last1=Bell |first1=SD |last2=Jackson |first2=SP |title=Transcription and translation in Archaea: a mosaic of eukaryal and bacterial features. |journal=Trends in Microbiology |date=June 1998 |volume=6 |issue=6 |pages=222–8 |pmid=9675798|doi=10.1016/S0966-842X(98)01281-5 }}</ref> They also use TFE, a TFIIE homolog, which assists in transcription initiation but is not required.<ref>{{cite journal |last1=Hanzelka |first1=BL |last2=Darcy |first2=TJ |last3=Reeve |first3=JN |title=TFE, an archaeal transcription factor in Methanobacterium thermoautotrophicum related to eucaryal transcription factor TFIIEalpha. |journal=Journal of Bacteriology |date=March 2001 |volume=183 |issue=5 |pages=1813–8 |doi=10.1128/JB.183.5.1813-1818.2001 |pmid=11160119|pmc=95073 }}</ref><ref>{{cite journal |last1=Gehring |first1=Alexandra M. |last2=Walker |first2=Julie E. |last3=Santangelo |first3=Thomas J. |last4=Margolin |first4=W. |title=Transcription Regulation in Archaea |journal=Journal of Bacteriology |date=15 July 2016 |volume=198 |issue=14 |pages=1906–1917 |doi=10.1128/JB.00255-16|pmid=27137495 |pmc=4936096 }}</ref>

=== RNA Polymerase I (Pol I) ===
{{main|RNA polymerase I#Initiation|}}

Formation of the Pol I preinitiation complex requires the binding of [[selective factor 1]] (SL1 or TIF-IB) to the core element of the [[Ribosomal DNA|rDNA]] promoter.<ref name=":0">{{Cite journal |last1=Friedrich |first1=J. Karsten |last2=Panov |first2=Kostya I. |last3=Cabart |first3=Pavel |last4=Russell |first4=Jackie |last5=Zomerdijk |first5=Joost C.B.M. |date=August 2005 |title=TBP-TAF Complex SL1 Directs RNA Polymerase I Pre-initiation Complex Formation and Stabilizes Upstream Binding Factor at the rDNA Promoter |journal=Journal of Biological Chemistry |volume=280 |issue=33 |pages=29551–29558 |doi=10.1074/jbc.m501595200 |pmid=15970593 |pmc=3858828 |issn=0021-9258 |doi-access=free }}</ref> SL1 is a complex composed of [[TATA-binding protein|TBP]] and at least three [[TBP-associated factors]] (TAFs). For basal levels of transcription, only SL1 and the initiation-competent form of [[RNA polymerase I|Pol I]] (Pol Iβ), characterized by [[RRN3]] binding, are required.<ref name=":1">{{Cite journal |last1=Russell |first1=Jackie |last2=Zomerdijk |first2=Joost C.B.M. |date=February 2005 |title=RNA-polymerase-I-directed rDNA transcription, life and works |url=http://dx.doi.org/10.1016/j.tibs.2004.12.008 |journal=Trends in Biochemical Sciences |volume=30 |issue=2 |pages=87–96 |doi=10.1016/j.tibs.2004.12.008 |pmid=15691654 |pmc=3858833 |issn=0968-0004}}</ref><ref name=":2">{{Citation |last1=Goodfellow |first1=Sarah J. |title=Basic Mechanisms in RNA Polymerase I Transcription of the Ribosomal RNA Genes |date=2012-06-28 |url=http://dx.doi.org/10.1007/978-94-007-4525-4_10 |pages=211–236 |access-date=2023-10-30 |place=Dordrecht |publisher=Springer Netherlands |isbn=978-94-007-4524-7 |last2=Zomerdijk |first2=Joost C. B. M.|series=Subcellular Biochemistry |volume=61 |doi=10.1007/978-94-007-4525-4_10 |pmid=23150253 |pmc=3855190 }}</ref>

For activated transcription levels, [[UBTF]] (UBF) is also required. UBTF binds as a dimer to both the upstream control element (UCE) and core element of the rDNA promoter, bending the DNA to form an [[enhanceosome]].<ref name=":2" /><ref name=":1" /> SL1 has been found to stabilize the binding of UBTF to the rDNA promoter.<ref name=":0" />

The subunits of the Pol I PIC differ between organisms.<ref name="grummt2003">{{cite journal |last1=Grummt |first1=Ingrid |date=15 July 2003 |title=Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus |journal=Genes & Development |volume=17 |issue=14 |pages=1691–1702 |doi=10.1101/gad.1098503R |pmid=12865296 |doi-access=free}}</ref>

=== RNA Polymerase III (Pol III) ===
{{main|RNA polymerase III#Initiation|}}

Pol III has three classes of initiation, which start with different factors recognizing different control elements but all converging on TFIIIB (similar to TFIIB-TBP; consists of TBP/TRF, a [[BRF1 (gene)|TFIIB-related factor]], and a [[BDP1|B″ unit]]) recruiting the Pol III preinitiation complex. The overall architecture resembles that of Pol II. Only TFIIIB needs to remain attached during elongation.<ref>{{cite journal |last1=Han |first1=Y |last2=Yan |first2=C |last3=Fishbain |first3=S |last4=Ivanov |first4=I |last5=He |first5=Y |title=Structural visualization of RNA polymerase III transcription machineries. |journal=Cell Discovery |date=2018 |volume=4 |article-number=40 |doi=10.1038/s41421-018-0044-z |pmid=30083386|pmc=6066478}}</ref>

== References ==
{{Reflist}}

== External links ==
*Descriptive image – [https://web.archive.org/web/19970715231755/http://www.biochem.ucl.ac.uk/bsm/xtal/teach/trans/pol2.gif biochem.ucl.ac.uk]

{{Cell signaling}}
{{Transcription}}

[[Category:Gene expression]]