miRNA processing

Definition

Target type: biologicalprocess

A process leading to the generation of a functional miRNA. Includes the cleavage of stem-loop RNA precursors into microRNAs (miRNAs). miRNAs are a class of small RNAs that primarily silence genes by blocking the translation of mRNA transcripts into protein, or by increasing the degradation of non-protein-coding RNA transcripts. [GOC:aruk, GOC:bc, GOC:dph, GOC:rl, GOC:tb, PMID:15066275, PMID:15066283, PMID:23985560, PMID:28379604]

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in regulating gene expression. The biogenesis of miRNAs is a complex process that involves multiple steps.

1. **Transcription:** miRNA genes are transcribed by RNA polymerase II to produce primary miRNAs (pri-miRNAs), which are long RNA transcripts containing the miRNA sequence. These pri-miRNAs are capped and polyadenylated, similar to messenger RNA (mRNA).

2. **Pri-miRNA processing:** The pri-miRNA is processed by the nuclear RNase III enzyme Drosha, which cleaves the pri-miRNA into a stem-loop structure called a pre-miRNA. This cleavage occurs in the nucleus, and the pre-miRNA is approximately 70 nucleotides long.

3. **Export:** The pre-miRNA is then exported from the nucleus to the cytoplasm by the export protein Exportin-5. This export requires the GTPase Ran, which is involved in nuclear transport.

4. **Pre-miRNA processing:** In the cytoplasm, the pre-miRNA is processed by another RNase III enzyme called Dicer. Dicer cleaves the pre-miRNA into a mature miRNA duplex, which is approximately 22 nucleotides long. This duplex has a 5' phosphate group and a 3' overhang.

5. **RISC loading:** The mature miRNA duplex is loaded into the RNA-induced silencing complex (RISC). The RISC is a multi-protein complex that includes the Argonaute protein. Within the RISC, one strand of the duplex, known as the guide strand, is selected and incorporated into the RISC. The other strand, the passenger strand, is usually degraded.

6. **Target recognition:** The guide strand within RISC binds to complementary sequences in target mRNAs. The binding of the guide strand to the target mRNA can result in translational repression, where protein synthesis is blocked, or mRNA degradation. miRNA targeting is often mediated by partial complementarity between the guide strand and the target mRNA.

7. **Gene silencing:** The binding of the miRNA to the target mRNA can lead to the silencing of gene expression. The specific outcome of miRNA-mediated gene silencing depends on the degree of complementarity between the miRNA and its target mRNA.

The biogenesis of miRNAs is a tightly regulated process, and defects in this pathway can contribute to various diseases.'
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Proteins (2)

Compounds (6)