negative regulation of transcription by RNA polymerase II

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. [GOC:go_curators, GOC:txnOH]

Negative regulation of transcription by RNA polymerase II is a complex process that involves a variety of mechanisms to control gene expression. The process is essential for maintaining cellular homeostasis and responding to changes in the environment. RNA polymerase II is the primary enzyme responsible for transcribing protein-coding genes in eukaryotic cells. The process of negative regulation of transcription by RNA polymerase II involves a series of steps that ultimately lead to a decrease in the amount of mRNA produced from a gene. This decrease in mRNA production can be achieved by inhibiting the initiation of transcription, promoting the termination of transcription, or destabilizing the mRNA itself.

**Mechanisms of Negative Regulation:**

* **Repressor Proteins:** Repressor proteins bind to specific DNA sequences called silencers, which are located upstream or downstream of the gene being regulated. Repressors block the binding of transcription factors to the promoter region, preventing the assembly of the transcription preinitiation complex. Some repressors may directly interact with RNA polymerase II, inhibiting its activity.

* **Chromatin Remodeling:** The structure of chromatin, the complex of DNA and proteins that makes up chromosomes, can significantly influence gene expression. Negative regulation can involve changes in chromatin structure that make the DNA less accessible to the transcription machinery. This can be achieved by modifications to histones, the proteins around which DNA is wrapped. Histone deacetylation, for example, leads to a more compact chromatin structure, reducing access to the DNA by transcription factors and RNA polymerase II.

* **MicroRNAs (miRNAs):** miRNAs are small, non-coding RNA molecules that can bind to target mRNAs and regulate their stability and translation. Some miRNAs bind to the 3' untranslated region (3'UTR) of target mRNAs, leading to their degradation or inhibition of their translation into proteins.

* **Long non-coding RNAs (lncRNAs):** lncRNAs are RNA molecules that are longer than 200 nucleotides and do not code for proteins. Some lncRNAs function as scaffolds for proteins, forming complexes that regulate gene expression. Others can directly bind to DNA or RNA, affecting transcription or translation.

* **DNA methylation:** Methylation of DNA is a chemical modification that can alter the accessibility of genes to the transcription machinery. Methylation patterns can be inherited and are influenced by environmental factors. DNA methylation is often associated with repression of gene expression.

**Consequences of Negative Regulation:**

* **Cellular Homeostasis:** Negative regulation ensures that genes are expressed at appropriate levels and in the correct tissues and at the right time. This is essential for maintaining cellular function and preventing uncontrolled growth.

* **Development and Differentiation:** Negative regulation plays a crucial role in developmental processes, including the differentiation of cells into specialized types.

* **Response to Environmental Signals:** Cells can respond to changes in their environment by altering gene expression. Negative regulation allows cells to turn off genes that are no longer needed or to downregulate their expression in response to stress or other stimuli.

**Dysregulation of Negative Regulation:**

Disruption of negative regulation can lead to a variety of diseases, including cancer, developmental disorders, and neurodegenerative disorders. For example, loss of function mutations in repressor proteins can lead to uncontrolled gene expression, contributing to cancer development.

**Conclusion:**

Negative regulation of transcription by RNA polymerase II is a highly sophisticated process that plays a central role in the regulation of gene expression. Understanding the mechanisms of negative regulation is essential for understanding the complexities of cellular function, development, and disease.'
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Proteins (190)

Compounds (4,198)