Transcription preinitiation complex

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The preinitiation complex (abbreviated PIC) is a large complex of proteins that is necessary for the transcription of protein-coding genes in eukaryotes (+archaea). The preinitiation complex helps position RNA polymerase II over 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 (co-activators and chromatin-remodeling complexes) could also be components of the PIC.

Assembly[edit]

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.
  • 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).

External links[edit]

References[edit]

  1. ^ Lee TI, Young RA (2000). "Transcription of eukaryotic protein-coding genes". Annu. Rev. Genet. 34: 77–137. doi:10.1146/annurev.genet.34.1.77. PMID 11092823. 
  2. ^ Kornberg RD (2007). "The molecular basis of eukaryotic transcription". Proc. Natl. Acad. Sci. U.S.A. 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 (1997). "Trajectory of DNA in the RNA polymerase II transcription preinitiation complex". Proc Natl Acad Sci USA 94 (23): 12268-73. doi:10.1073/pnas.94.23.12268. PMC 24903. PMID 9356438. 
  4. ^ Kim TK, Ebright RH, Reinberg D (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.