transcription initiation at RNA polymerase I promoter

Definition

Target type: biologicalprocess

A transcription initiation process that takes place at a RNA polymerase I gene promoter. Ribosomal RNAs (rRNA) genes are transcribed by RNA polymerase I. [GOC:txnOH]

Transcription initiation at the RNA polymerase I (Pol I) promoter is a complex and highly regulated process that involves a cascade of protein interactions and conformational changes. It is essential for the synthesis of ribosomal RNA (rRNA), which is the main component of ribosomes, the cellular machinery responsible for protein synthesis.

The Pol I promoter, located in the ribosomal DNA (rDNA) gene cluster, is a specialized structure that differs significantly from the promoters recognized by Pol II and Pol III. It is typically defined by a core promoter element, the core element (CE), located approximately 40 bp upstream of the transcription start site, and an upstream control element (UCE), located 100-200 bp upstream of the CE.

The process of transcription initiation at the Pol I promoter can be summarized as follows:

1. **Assembly of the pre-initiation complex (PIC):** The first step involves the recruitment of the transcription factor TBP (TATA-binding protein) to the CE. TBP, in complex with the TBP-associated factors (TAFs), forms the TFIID complex, which serves as a scaffold for the assembly of other transcription factors. The UBF (upstream binding factor) binds to the UCE and interacts with TFIID, further stabilizing the complex.

2. **Recruitment of Pol I:** Once the TFIID-UBF complex is established, the Pol I enzyme is recruited to the promoter. Pol I, together with its associated factors, SL1 (selectivity factor 1), forms a stable complex that is competent for initiation. SL1 is a multi-subunit complex containing TAF1, TAF1B, TAF1C, and TBP. TAF1C and TBP bind to the core promoter, while TAF1 and TAF1B interact with UBF.

3. **DNA melting and initiation of transcription:** Upon Pol I binding, the DNA template is unwound, creating a transcription bubble, and the first phosphodiester bond is formed. This step is facilitated by the activity of the Pol I subunit RPB1, which possesses helicase activity.

4. **Escape from the promoter:** After the initiation complex is formed and the first few nucleotides are synthesized, the Pol I enzyme dissociates from the promoter and translocates along the DNA template, extending the nascent RNA chain.

The regulation of Pol I transcription is crucial for maintaining cellular homeostasis and ensuring efficient protein synthesis. Factors that regulate Pol I transcription include:

- **Nucleolar localization:** Transcription of rDNA occurs in the nucleolus, a specialized nuclear compartment enriched in rRNA and ribosomal proteins. This localization is essential for the efficient assembly of ribosomes.

- **Upstream control elements (UCE):** The UCEs in the rDNA are highly conserved sequences that bind to UBF, a transcription factor critical for Pol I activity. UBF interacts with SL1 and TFIID, mediating the assembly of the pre-initiation complex and promoting transcription initiation.

- **Growth factors and nutrient availability:** Pol I transcription is responsive to growth signals and nutrient availability. For example, growth factors like insulin and IGF-1 stimulate Pol I activity, leading to increased rRNA synthesis and protein production.

- **Stress responses:** In response to stress, such as DNA damage or nutrient deprivation, Pol I transcription is often downregulated. This helps to conserve cellular resources and protect the cell from further damage.

- **Post-transcriptional modifications:** Once the rRNA transcript is synthesized, it undergoes extensive post-transcriptional processing, including methylation, pseudouridylation, and cleavage. These modifications are crucial for the correct folding and assembly of rRNA into functional ribosomes.

In summary, transcription initiation at the Pol I promoter is a highly regulated process that involves the coordinated action of multiple transcription factors and regulatory elements. This process ensures the efficient production of rRNA, which is essential for the proper functioning of ribosomes and protein synthesis.'
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Proteins (1)

Compounds (3)