positive regulation of primary miRNA processing

Definition

Target type: biologicalprocess

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

Positive regulation of primary miRNA processing is a crucial step in the biogenesis of microRNAs (miRNAs), which are small non-coding RNAs that play a vital role in regulating gene expression. Primary miRNAs (pri-miRNAs) are transcribed from DNA as long precursor molecules with hairpin-like structures. These pri-miRNAs are then processed by a complex machinery to produce mature miRNAs that can silence target mRNAs. This intricate process involves several key players and steps:

1. **Transcription of pri-miRNAs:** The first step involves the transcription of pri-miRNAs from their corresponding genes by RNA polymerase II. These pri-miRNAs are typically several kilobases long and contain a characteristic stem-loop structure.
2. **Recognition and cleavage by Drosha:** Once transcribed, pri-miRNAs are recognized and cleaved by a microprocessor complex containing the RNase III enzyme Drosha and its partner protein DGCR8. Drosha specifically cleaves the pri-miRNA at the base of the stem-loop structure, generating a shorter precursor molecule called a pre-miRNA.
3. **Export to the cytoplasm:** The pre-miRNA, approximately 70 nucleotides in length, is then exported from the nucleus to the cytoplasm by the exportin-5 protein.
4. **Processing by Dicer:** In the cytoplasm, the pre-miRNA is further processed by another RNase III enzyme called Dicer, which cleaves the stem-loop structure to generate a double-stranded RNA (dsRNA) molecule of approximately 22 nucleotides.
5. **Unwinding and loading into RISC:** The dsRNA is then unwound by an enzyme called helicase, and one of the strands, the guide strand, is incorporated into the RNA-induced silencing complex (RISC). This complex is composed of several proteins, including Argonaute (Ago) proteins.
6. **Target mRNA silencing:** The mature miRNA within the RISC complex then binds to its target mRNA through complementary base pairing. This binding can lead to translational repression or mRNA degradation, ultimately silencing the target gene.

Positive regulation of this process involves factors that enhance the expression of pri-miRNAs, promote their efficient processing by Drosha and Dicer, and facilitate their transport to the cytoplasm. These factors can include:

* **Transcriptional activators:** Transcription factors that bind to the promoter regions of pri-miRNA genes can increase their transcription rates, leading to higher levels of pri-miRNAs.
* **Microprocessor complex components:** Factors that enhance the activity or stability of Drosha or DGCR8 can improve pri-miRNA processing.
* **Exportin-5:** Factors that promote the interaction of pre-miRNAs with exportin-5 can ensure efficient transport to the cytoplasm.
* **Dicer:** Factors that increase the expression or activity of Dicer can accelerate pre-miRNA processing.
* **RISC components:** Factors that enhance the assembly or stability of the RISC complex can facilitate target mRNA silencing.

Dysregulation of positive regulation of primary miRNA processing can have significant consequences for cellular functions. For example, increased levels of certain miRNAs can contribute to the development of cancer, while decreased levels of others can lead to developmental defects. Therefore, understanding the regulatory mechanisms governing miRNA biogenesis is crucial for comprehending normal cellular processes and developing strategies to treat diseases.'"

Proteins (1)

Compounds (3)