The initiation is in the molecular biology of the first step of the transcription , in which a DNA -dependent RNA polymerase, an RNA synthesized (prepared), the sequence (nucleotide sequence) required by the DNA.
In the case of prokaryotes , initiation proceeds as follows:
A protein, the so-called sigma factor , binds to the Pribnow box of the promoter and thus drastically increases the probability of the polymerase binding at this point. The elongation is now started with the incorporation of nucleotides , with the sigma factor being split off.
First, the so-called TFIID binds to the DNA, where TF stands for transcription factor , II for polymerase II and D names the factor itself. TFIID consists of two components: a) the TATA-binding protein (TBP), which recognizes the TATA box and binds to it, and b) TBP-associated factors, many small proteins (TAFs), which recognize TATA-less promoters. A TFIIA now binds to the promoter, which stabilizes TFIID. It now associates the TFIIB , which ensures that the polymerase II can be bound. The TFIIF now leads the polymerase II to the promoter. In the end, the TFIIE is still missing, which enables the TFIIH to dock . The TFIIH has helicase and protein kinase activity. The helicase unwinds the DNA strand just before and in the polymerase. The latter, on the other hand, phosphorylates the carboxy-terminal domain (CTD) of the polymerase, which after the start of mRNA construction leads to the binding of the pre-initiation complex with the core promoter being broken.
When the complex is formed, the DNA template is brought up to the catalytic center of the RNA polymerase (RPB1 / RPB2). This facilitates the formation of the first phosphodiester bond, with which transcription begins. As a result, the TFIIB subunit separates from the pre-initiation complex. At this point in time, the open configuration can still change to the closed configuration if, for example, there is no ATP supply to the TFIIH or if there are inhibiting factors.
Separation from the promoter
As with the prokaryotes, nucleotides are now incorporated with cleavage of pyrophosphate. The formation of the second phosphodiester bond leads to a 3-base mRNA, and the open loop now extends from −9 to +3 with respect to the start of transcription. After incorporation of the fourth nucleotide, a deficiency in ATP in the TFIIH subunit no longer causes the loop to collapse. The separation from the promoter can no longer be reversed, the TFIIB subunit dissociates from the overall complex. During the incorporation of nucleotide five to ten, a cap structure is attached to the 5 'end of the mRNA, which protects it from enzymes and is a recognition signal for splicing and transport out of the cell nucleus. The elongation begins with nucleotide eleven and only TFIIH remains complexed with the polymerase.
- Reinberg / reactome: RNA Polymerase II Transcription Pre-Initiation ( page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.
- Kornberg RD: The molecular basis of eukaryotic transcription . In: Proc. Natl. Acad. Sci. USA . 104, No. 32, 2007, pp. 12955-61. doi : 10.1073 / pnas.0704138104 . PMID 17670940 .
- Timmers / reactome: RNA Polymerase II Transcription Initiation ( page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.
- Timmers / reactome: RNA Polymerase II Promoter Escape ( page no longer available , search in web archives ) Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.