negative regulation of transcription elongation by RNA polymerase II

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of transcription elongation, the extension of an RNA molecule after transcription initiation and promoter clearance by the addition of ribonucleotides, catalyzed by RNA polymerase II. [GOC:mah, GOC:txnOH]

Negative regulation of transcription elongation by RNA polymerase II is a crucial process that controls the rate and efficiency of gene expression. This regulation is achieved through a complex interplay of factors that bind to DNA and RNA polymerase II, influencing the progression of the transcription machinery along the gene.

**Key Players:**

* **RNA Polymerase II:** The central enzyme responsible for transcribing DNA into RNA.
* **Transcription Elongation Factors (TEFs):** Proteins that associate with RNA polymerase II and facilitate its movement along the DNA template.
* **Negative Regulators:** These proteins act as brakes on transcription elongation, slowing down or halting the progress of RNA polymerase II.

**Mechanisms of Negative Regulation:**

1. **Chromatin Remodeling:** The structure of chromatin, the complex of DNA and proteins, can influence transcription elongation. Tightly packed chromatin hinders the access of RNA polymerase II to the DNA template, thereby suppressing transcription.
2. **Recruitment of Repressor Proteins:** Certain proteins bind to DNA sequences within the gene or to RNA polymerase II itself, directly inhibiting its elongation activity. These repressors can act by:
* **Blocking the progression of RNA polymerase II:** They physically obstruct the movement of the polymerase along the DNA.
* **Altering the conformation of RNA polymerase II:** They induce conformational changes in the polymerase that make it less efficient in elongating the RNA transcript.
* **Recruiting other inhibitory factors:** Repressors can attract other proteins that further suppress transcription elongation.
3. **Post-Translational Modifications:** Modifications to the tail of RNA polymerase II can impact its elongation activity. For instance, phosphorylation of certain residues can promote elongation, while dephosphorylation can hinder it.
4. **RNA Processing:** The processing of the nascent RNA transcript, including splicing and capping, can also influence the rate of transcription elongation. Defects in these processes can lead to premature termination of transcription.

**Biological Significance:**

* **Fine-tuning Gene Expression:** Negative regulation of transcription elongation ensures that genes are expressed at appropriate levels in different cells and tissues, under varying physiological conditions.
* **Preventing Uncontrolled Transcription:** It safeguards against the transcription of unwanted or potentially harmful genes.
* **Cell Differentiation and Development:** It plays a crucial role in the precise regulation of gene expression during development and differentiation.

**Dysregulation and Disease:**

Disruptions in the negative regulation of transcription elongation can contribute to a wide range of diseases, including cancer, developmental disorders, and neurodegenerative diseases. Understanding the mechanisms underlying this regulation is crucial for developing therapeutic strategies to target these conditions.'
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Proteins (6)

Compounds (80)