regulation of miRNA processing

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of microRNA processing. [GO_REF:0000058, GOC:BHF, GOC:BHF_miRNA, GOC:rph, GOC:TermGenie, PMID:22269326]

MicroRNA (miRNA) processing is a complex and tightly regulated process that involves a series of steps, each with its own set of regulatory mechanisms. miRNAs are small, non-coding RNA molecules that play a crucial role in gene regulation. They act by binding to the 3'-untranslated region (3'UTR) of target mRNAs, leading to either translational repression or mRNA degradation.

The process begins with the transcription of a primary miRNA (pri-miRNA) by RNA polymerase II, a process that is influenced by various transcription factors. This pri-miRNA is a long, stem-loop structure that is then processed in the nucleus by the Microprocessor complex, which consists of the RNase III enzyme Drosha and its cofactor DGCR8. Drosha cleaves the pri-miRNA, releasing a shorter precursor miRNA (pre-miRNA) that is approximately 70 nucleotides long.

The pre-miRNA is then exported from the nucleus to the cytoplasm by Exportin-5. In the cytoplasm, the pre-miRNA is further processed by another RNase III enzyme called Dicer. Dicer removes the terminal loop of the pre-miRNA, generating a mature miRNA duplex, which is approximately 22 nucleotides long. This duplex consists of two strands, a guide strand and a passenger strand.

The mature miRNA duplex is then loaded onto a protein complex called the RNA-induced silencing complex (RISC). Within RISC, the passenger strand is degraded, while the guide strand remains associated with the complex. This guide strand is then able to bind to complementary sequences in the 3'UTR of target mRNAs, leading to their translational repression or degradation.

The regulation of miRNA processing is crucial for maintaining cellular homeostasis and responding to various stimuli. The process can be regulated at multiple levels, including:

1. **Transcriptional regulation:** Transcription factors can bind to the promoters of miRNA genes, controlling their expression levels.
2. **Processing by Drosha and Dicer:** The activity of Drosha and Dicer can be regulated by various factors, including post-translational modifications, protein-protein interactions, and small molecule inhibitors.
3. **Export of pre-miRNA:** The export of pre-miRNA from the nucleus is regulated by Exportin-5, which can be modulated by various cellular signals.
4. **Loading onto RISC:** The loading of mature miRNA duplex onto RISC is a dynamic process that is influenced by factors such as the availability of RISC components and the sequence of the miRNA.
5. **Target recognition and silencing:** The efficiency of miRNA-mediated target silencing can be influenced by factors such as the degree of complementarity between the miRNA and its target mRNA, the availability of other regulatory proteins, and the cellular context.

Dysregulation of miRNA processing can lead to various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. This is because miRNAs play a critical role in regulating a wide range of cellular processes. Therefore, understanding the mechanisms of miRNA processing regulation is crucial for developing novel therapeutic strategies for these diseases.'"

Proteins (1)

Compounds (2)