Transcription preinitiation complex
The preinitiation complex (abbreviated PIC) is a complex of approximately 100 proteins that is necessary for the transcription of protein-coding genes in eukaryotes and archaea. The preinitiation complex positions RNA polymerase II (Pol II) at gene transcription start sites, denatures the DNA, and positions the DNA in the RNA polymerase II active site for transcription.[1][2][3][4]
![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.](http://upload.wikimedia.org/wikipedia/commons/thumb/8/82/Figure_16_04_01.jpg/220px-Figure_16_04_01.jpg)
The minimal PIC includes RNA polymerase II and six general transcription factors: TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. Additional regulatory complexes (such as the mediator coactivator[5] and 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)
editA classical view of PIC formation at the promoter involves the following steps:
- TATA binding protein (TBP, a subunit of TFIID) binds the promoter, creating a sharp bend in the promoter DNA.[6]
- 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 superhelical tension in the DNA.
- Negative superhelical tension causes approximately one turn of DNA to 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
editIn Archaea
editArchaea 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.[8] They also use TFE, a TFIIE homolog, which assists in transcription initiation but is not required.[9][10]
RNA Polymerase I (Pol I)
editFormation of the Pol I preinitiation complex requires the binding of selective factor 1 (SL1 or TIF-IB) to the core element of the rDNA promoter.[11] SL1 is a complex composed of TBP and at least three TBP-associated factors (TAFs). For basal levels of transcription, only SL1 and the initiation-competent form of Pol I (Pol Iβ), characterized by RRN3 binding, are required.[12][13]
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.[13][12] SL1 has been found to stabilize the binding of UBTF to the rDNA promoter.[11]
The subunits of the Pol I PIC differ between organisms.[14]
RNA Polymerase III (Pol III)
editPol 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 TFIIB-related factor, and a B″ unit) recruiting the Pol III preinitiation complex. The overall architecture resembles that of Pol II. Only TFIIIB needs to remain attached during elongation.[15]
References
edit- ^ Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annual Review of Genetics. 34: 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823.
- ^ Kornberg RD (August 2007). "The molecular basis of eukaryotic transcription". Proceedings of the National Academy of Sciences of the United States of America. 104 (32): 12955–61. Bibcode:2007PNAS..10412955K. doi:10.1073/pnas.0704138104. PMC 1941834. PMID 17670940.
- ^ Kim TK, Lagrange T, Wang YH, Griffith JD, Reinberg D, Ebright RH (November 1997). "Trajectory of DNA in the RNA polymerase II transcription preinitiation complex". Proceedings of the National Academy of Sciences of the United States of America. 94 (23): 12268–73. Bibcode:1997PNAS...9412268K. doi:10.1073/pnas.94.23.12268. PMC 24903. PMID 9356438.
- ^ Kim TK, Ebright RH, Reinberg D (May 2000). "Mechanism of ATP-dependent promoter melting by transcription factor IIH". Science. 288 (5470): 1418–22. Bibcode:2000Sci...288.1418K. doi:10.1126/science.288.5470.1418. PMID 10827951.
- ^ Allen BL, Taatjes DJ (2015). "The Mediator complex: a central integrator of transcription". Nature Reviews. Molecular Cell Biology. 16 (3): 155–66. doi:10.1038/nrm3951. PMC 4963239. PMID 25693131.
- ^ Ossipow, Vincent; Fonjallaz, Philippe; Schibler, Ueli (1999-02-01). "An RNA Polymerase II Complex Containing All Essential Initiation Factors Binds to the Activation Domain of PAR Leucine Zipper Transcription Factor Thyroid Embryonic Factor". Molecular and Cellular Biology. 19 (2): 1242–1250. doi:10.1128/MCB.19.2.1242. ISSN 1098-5549. PMC 116053. PMID 9891058.
- ^ Duttke, SH (March 2015). "Evolution and diversification of the basal transcription machinery". Trends in Biochemical Sciences. 40 (3): 127–9. doi:10.1016/j.tibs.2015.01.005. PMC 4410091. PMID 25661246.
- ^ Bell, SD; Jackson, SP (June 1998). "Transcription and translation in Archaea: a mosaic of eukaryal and bacterial features". Trends in Microbiology. 6 (6): 222–8. doi:10.1016/S0966-842X(98)01281-5. PMID 9675798.
- ^ Hanzelka, BL; Darcy, TJ; Reeve, JN (March 2001). "TFE, an archaeal transcription factor in Methanobacterium thermoautotrophicum related to eucaryal transcription factor TFIIEalpha". Journal of Bacteriology. 183 (5): 1813–8. doi:10.1128/JB.183.5.1813-1818.2001. PMC 95073. PMID 11160119.
- ^ Gehring, Alexandra M.; Walker, Julie E.; Santangelo, Thomas J.; Margolin, W. (15 July 2016). "Transcription Regulation in Archaea". Journal of Bacteriology. 198 (14): 1906–1917. doi:10.1128/JB.00255-16. PMC 4936096. PMID 27137495.
- ^ a b Friedrich, J. Karsten; Panov, Kostya I.; Cabart, Pavel; Russell, Jackie; Zomerdijk, Joost C.B.M. (August 2005). "TBP-TAF Complex SL1 Directs RNA Polymerase I Pre-initiation Complex Formation and Stabilizes Upstream Binding Factor at the rDNA Promoter". Journal of Biological Chemistry. 280 (33): 29551–29558. doi:10.1074/jbc.m501595200. ISSN 0021-9258. PMC 3858828. PMID 15970593.
- ^ a b Russell, Jackie; Zomerdijk, Joost C.B.M. (February 2005). "RNA-polymerase-I-directed rDNA transcription, life and works". Trends in Biochemical Sciences. 30 (2): 87–96. doi:10.1016/j.tibs.2004.12.008. ISSN 0968-0004. PMC 3858833. PMID 15691654.
- ^ a b Goodfellow, Sarah J.; Zomerdijk, Joost C. B. M. (2012-06-28), Basic Mechanisms in RNA Polymerase I Transcription of the Ribosomal RNA Genes, Subcellular Biochemistry, vol. 61, Dordrecht: Springer Netherlands, pp. 211–236, doi:10.1007/978-94-007-4525-4_10, ISBN 978-94-007-4524-7, PMC 3855190, PMID 23150253, retrieved 2023-10-30
- ^ Grummt, Ingrid (15 July 2003). "Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus". Genes & Development. 17 (14): 1691–1702. doi:10.1101/gad.1098503R. PMID 12865296.
- ^ Han, Y; Yan, C; Fishbain, S; Ivanov, I; He, Y (2018). "Structural visualization of RNA polymerase III transcription machineries". Cell Discovery. 4: 40. doi:10.1038/s41421-018-0044-z. PMC 6066478. PMID 30083386.
External links
edit- Descriptive image – biochem.ucl.ac.uk