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 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]

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.

Assembly

A 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.
  • TBP-TFIIA interactions recruit TFIIA to the promoter.
  • TBP-TFIIB interactions recruit TFIIB to the promoter.
  • TFIIB-RNA polymerase II and TFIIB-TFIIF interactions recruit 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).

References

  1. ↑ 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.
  2. ↑ 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. doi:10.1073/pnas.0704138104. PMC 1941834. PMID 17670940.
  3. ↑ 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. doi:10.1073/pnas.94.23.12268. PMC 24903. PMID 9356438.
  4. ↑ Kim TK, Ebright RH, Reinberg D (May 2000). "Mechanism of ATP-dependent promoter melting by transcription factor IIH". Science. 288 (5470): 1418–22. doi:10.1126/science.288.5470.1418. PMID 10827951.
  5. ↑ 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.
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