negative regulation of miRNA transcription

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of microRNA (miRNA) gene transcription. [GO_REF:0000058, GOC:dph, GOC:kmv, GOC:TermGenie, PMID:24699545]

Negative regulation of miRNA transcription is a complex process that fine-tunes the expression of microRNAs (miRNAs), small non-coding RNAs that play crucial roles in gene regulation. This process involves a diverse array of molecular mechanisms aimed at reducing the production of primary miRNAs (pri-miRNAs), the precursors of mature miRNAs.

**Key Players:**

* **Transcription Factors:** These proteins bind to specific DNA sequences within miRNA gene promoters, either activating or repressing transcription. Repressor proteins, like the REST family, can directly bind to miRNA promoters, hindering the recruitment of RNA polymerase II and preventing pri-miRNA synthesis.

* **Epigenetic Modifications:** Changes in chromatin structure, such as DNA methylation and histone modifications, can influence miRNA gene accessibility and transcription. Hypermethylation of miRNA promoters can lead to silencing, while histone deacetylation can condense chromatin, making it less accessible to transcription machinery.

* **MicroRNAs Themselves:** miRNAs can also regulate their own transcription through a feedback loop. A mature miRNA may target the mRNA of its own gene, leading to a reduction in its own production. This negative feedback mechanism helps maintain miRNA levels within a specific range.

* **Non-coding RNAs (ncRNAs):** Long non-coding RNAs (lncRNAs) can act as scaffolds, interacting with proteins involved in gene regulation. Certain lncRNAs can bind to miRNA promoters, directly repressing transcription or influencing the recruitment of transcription factors.

**Mechanisms of Negative Regulation:**

* **Direct Inhibition of Transcription:** Transcription factors like REST directly bind to miRNA promoters, blocking the binding of RNA polymerase II and preventing pri-miRNA synthesis.
* **Chromatin Remodeling:** Epigenetic modifications, such as DNA methylation and histone deacetylation, can alter the chromatin structure around miRNA genes, making them less accessible to transcription machinery.
* **Post-Transcriptional Regulation:** Some mechanisms target the pri-miRNA after it has been transcribed, preventing its processing into mature miRNAs. This can involve interactions with proteins that block the activity of Drosha, an enzyme involved in pri-miRNA processing.
* **Feedback Loops:** Mature miRNAs can bind to their own mRNA, leading to a reduction in their own production. This negative feedback loop ensures tight regulation of miRNA expression.

**Significance:**

* **Fine-Tuning Gene Expression:** Negative regulation of miRNA transcription is essential for fine-tuning gene expression in various cellular processes. By modulating miRNA levels, cells can respond to diverse stimuli and maintain homeostasis.
* **Disease Development:** Dysregulation of miRNA transcription has been implicated in a wide range of diseases, including cancer, cardiovascular diseases, and neurological disorders. Aberrant miRNA expression can disrupt normal cellular processes and contribute to disease development.

**Overall, negative regulation of miRNA transcription is a multifaceted process that involves a complex interplay of transcription factors, epigenetic modifications, and regulatory RNAs. This intricate regulation ensures precise control over miRNA levels, contributing to the maintenance of cellular function and the prevention of disease.**'
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Proteins (13)

Compounds (492)