negative regulation of gene expression

Definition

Target type: biologicalprocess

Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). [GOC:txnOH-2018]

Negative regulation of gene expression is a fundamental process that controls the level of gene products, including proteins and RNA, within a cell. It involves a complex interplay of molecular mechanisms that act to suppress or reduce the expression of specific genes. This intricate regulatory network is essential for maintaining cellular homeostasis, responding to environmental stimuli, and ensuring proper development and function.

**Key Mechanisms of Negative Regulation:**

* **Transcriptional Repression:** This involves blocking the initiation of transcription, the process of copying DNA into RNA. Repressor proteins bind to specific DNA sequences, known as promoter regions, upstream of the gene, preventing the recruitment of RNA polymerase, the enzyme responsible for transcription.

* **Post-Transcriptional Regulation:** This encompasses mechanisms that control the stability and translation of messenger RNA (mRNA), the template for protein synthesis. MicroRNAs (miRNAs) are small RNA molecules that can bind to mRNA and target it for degradation or block its translation. Other mechanisms include RNA-binding proteins that can influence mRNA stability, splicing, and localization.

* **Translational Repression:** This mechanism inhibits the translation of mRNA into protein. Certain proteins can bind to the mRNA and prevent ribosomes, the protein synthesis machinery, from accessing it.

* **Protein Degradation:** This involves the breakdown of proteins after they are synthesized. Proteasomes are cellular machines that degrade proteins tagged with ubiquitin, a small protein that acts as a signal for degradation.

**Biological Significance:**

Negative regulation of gene expression plays crucial roles in a wide range of biological processes, including:

* **Cell Differentiation:** The precise regulation of gene expression is essential for directing cells to develop into specialized cell types.
* **Immune Response:** Negative regulation is crucial for controlling the intensity and duration of immune responses to prevent excessive inflammation and autoimmunity.
* **Development:** Precise control of gene expression is essential for normal embryonic development and organ formation.
* **Disease Processes:** Dysregulation of gene expression can contribute to the development of various diseases, including cancer, metabolic disorders, and neurodegenerative diseases.

**Examples of Negative Regulation:**

* **The lac Operon in Bacteria:** In bacteria, the lac operon is a classic example of negative regulation. When lactose is absent, a repressor protein binds to the operon and blocks transcription of the genes needed for lactose metabolism.
* **The p53 Tumor Suppressor Gene:** The p53 gene is a key regulator of cell cycle arrest and apoptosis in response to DNA damage. Its expression is negatively regulated by the MDM2 protein, preventing excessive p53 activity.

In conclusion, negative regulation of gene expression is an intricate and essential process that fine-tunes cellular function by controlling the levels of gene products. Its disruption can have profound consequences for cellular homeostasis and disease development.'
"

Proteins (86)

Compounds (3,916)