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RNA polymerase I preinitiation complex assembly

Definition

Target type: biologicalprocess

The formation of a large multiprotein-DNA complex that self-assembles on gene promoter through the sequential recruitment of the general initiation factors that compose the preinitiation complex (PIC) (which includes including UBF, SL1, RRN3 and TBP in human). The PIC engages RNA polymerase I on its DNA template strand and sparks polymerization of the first few RNA nucleotides. [GOC:txnOH, PMID:14969726]

The assembly of the RNA polymerase I (Pol I) preinitiation complex (PIC) is a highly orchestrated process that involves the sequential recruitment of multiple factors to the ribosomal DNA (rDNA) promoter. This process is essential for the transcription of ribosomal RNA (rRNA), a fundamental component of ribosomes, the protein synthesis machinery. Here's a detailed description of the steps involved:

1. **rDNA Promoter Recognition:** The process begins with the binding of the transcription factor UBF (Upstream Binding Factor) to the rDNA promoter. UBF binds to two distinct regions within the promoter: the core element and the upstream control element. The core element is a short sequence that is essential for the binding of other factors, while the upstream control element modulates the efficiency of transcription initiation.

2. **SL1 Assembly:** UBF recruits the SL1 complex, a four-subunit complex consisting of TBP (TATA-binding protein) and three TAFs (TBP-associated factors). SL1 binds to the core element of the promoter and positions TBP within the minor groove of the DNA. TBP is a key factor in the recruitment of Pol I to the promoter.

3. **Pol I Recruitment:** Pol I is then recruited to the promoter by interacting with SL1 and UBF. Pol I associates with the DNA via its two largest subunits, RPB1 and RPB2.

4. **rDNA Looping and Preinitiation Complex Stabilization:** The binding of Pol I to the promoter is further stabilized by the formation of a DNA loop between the core element and the upstream control element. This looping is mediated by the interaction of UBF bound to these two regions.

5. **Preinitiation Complex Activation:** The preinitiation complex is now ready for transcription initiation. The process is further facilitated by the phosphorylation of the C-terminal domain (CTD) of the Pol I largest subunit (RPB1). This phosphorylation is carried out by a kinase known as CDK9.

6. **Transcription Initiation:** The activated Pol I PIC then initiates transcription by unwinding the DNA and incorporating the first few nucleotides of the rRNA transcript.

In summary, the assembly of the Pol I PIC involves a series of sequential interactions between various factors, including UBF, SL1, and Pol I. This process results in the formation of a stable and active complex that is capable of initiating transcription of rRNA genes. These genes are crucial for the production of ribosomes, which are essential for protein synthesis and the growth and development of all living organisms.'
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Proteins (2)

ProteinDefinitionTaxonomy
Bromodomain adjacent to zinc finger domain protein 2AA bromodomain adjacent to zinc finger domain protein 2A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UIF9]Homo sapiens (human)
Transcription activator BRG1A transcription activator BRG1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P51532]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
i-bet726
pf-06687252PF-06687252: a SMARCA2/4 bromodomain inhibitor; structure in first source

PFI-3 : An azabicycloalkane that is (1R,4R)-2,5-diazabicyclo[2.2.1]heptane which is substituted at position 2 by a 3-(2-hydroxyphenyl)-3-oxoprop-1-en-1-yl group and at position 5 by a pyridin-2-yl group. It is a potent and selective inhibitor of polybromo 1 (Kd = 48 nM), SMARCA2 and SMARCA4 (Kd = 89 nM) bromodomains.
azabicycloalkane;
enone;
phenols;
pyridines