negative regulation of primary miRNA processing

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of primary microRNA processing. [GOC:dph, GOC:sl]

Negative regulation of primary miRNA processing involves a complex interplay of factors that modulate the production of mature miRNAs. These miRNAs play crucial roles in gene regulation, influencing a wide range of cellular processes. The process begins with the transcription of a primary miRNA (pri-miRNA) transcript by RNA polymerase II. This pri-miRNA is a long RNA molecule containing the hairpin structure that will eventually give rise to the mature miRNA. The first step in negative regulation is the inhibition of pri-miRNA transcription. This can be achieved by various mechanisms, including:
* **Repression of the miRNA gene promoter:** Transcription factors can bind to the promoter region of the miRNA gene, blocking the recruitment of RNA polymerase II and preventing transcription.
* **Chromatin modifications:** Modifications like methylation and acetylation of histones in the chromatin surrounding the miRNA gene can affect its accessibility to transcription machinery.
* **RNA polymerase II inhibition:** Factors that directly inhibit the activity of RNA polymerase II can also reduce pri-miRNA transcription.

Once a pri-miRNA transcript is produced, its processing can be further regulated. Several key players are involved in this step:
* **Drosha-DGCR8 complex:** This complex is responsible for cleaving the pri-miRNA in the nucleus, generating a shorter precursor miRNA (pre-miRNA) hairpin.
* **Exportin-5:** This protein escorts the pre-miRNA from the nucleus to the cytoplasm.
* **Dicer:** This enzyme cleaves the pre-miRNA in the cytoplasm, generating a mature miRNA duplex.
* **RISC complex:** The mature miRNA duplex is loaded into the RISC complex, where one strand is incorporated and the other is degraded.

Negative regulation can occur at each of these processing steps:
* **Drosha-DGCR8 inhibition:** Certain proteins can interact with the Drosha-DGCR8 complex, inhibiting its activity and reducing the production of pre-miRNA.
* **Exportin-5 inhibition:** Factors that block the export of pre-miRNAs from the nucleus can hinder their processing into mature miRNAs.
* **Dicer inhibition:** Proteins that bind to Dicer or interfere with its catalytic activity can inhibit the cleavage of pre-miRNAs.
* **RISC loading inhibition:** Factors that prevent the proper loading of mature miRNAs into the RISC complex can disrupt the downstream silencing functions of the miRNA.

The negative regulation of primary miRNA processing is essential for maintaining proper cellular homeostasis. Dysregulation of this process can lead to aberrant miRNA expression and contribute to various diseases, including cancer and developmental disorders. Understanding the mechanisms involved in this regulation is crucial for developing therapeutic strategies targeting miRNA pathways.'
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Proteins (2)

Compounds (30)