siRNA processing

Definition

Target type: biologicalprocess

A process leading to the generation of a functional small interfering RNA (siRNA). Includes the cleavage of double-stranded RNA to form small interfering RNA molecules (siRNAs) of 21-23 nucleotides. May also include amplification of the siRNA by RNA-directed RNA polymerase. [GOC:mah, PMID:11524674, PMID:19239886, PMID:20687832]

siRNA processing is a crucial step in the RNA interference (RNAi) pathway, a natural defense mechanism in eukaryotes that regulates gene expression. The process involves the following key steps:

1. **siRNA Synthesis:**
- **dsRNA Cleavage:** The process begins with the introduction of double-stranded RNA (dsRNA) into the cell. This dsRNA can be introduced exogenously or produced endogenously by the cell itself. Dicer, a ribonuclease enzyme, recognizes and cleaves the dsRNA into short, double-stranded fragments called small interfering RNA (siRNA).
- **siRNA Structure:** Each siRNA molecule is typically 21-23 nucleotides long and has a characteristic structure:
- **5' Phosphate Group:** On one end of the siRNA molecule is a phosphate group.
- **3' Hydroxyl Group:** On the other end is a hydroxyl group.
- **Sense and Antisense Strands:** The siRNA molecule consists of two strands: a sense strand (which has the same sequence as the target mRNA) and an antisense strand (which is complementary to the target mRNA).

2. **RISC Assembly:**
- **RISC Loading:** The siRNA molecules associate with a multi-protein complex called the RNA-induced silencing complex (RISC).
- **Strand Selection:** Within RISC, one strand of the siRNA (typically the antisense strand) is selected as the guide strand. This strand will direct RISC to the target mRNA. The other strand (the sense strand) is degraded.
- **RISC Activation:** RISC becomes activated and ready to target mRNA.

3. **mRNA Targeting and Degradation:**
- **Target Recognition:** The guide strand within RISC base-pairs with the complementary sequence in the target mRNA.
- **Cleavage:** The activated RISC complex cleaves the target mRNA at a specific site, typically 10-11 nucleotides downstream of the 5' end of the guide strand.
- **mRNA Degradation:** The cleaved mRNA is then degraded by cellular enzymes, preventing translation into protein.

4. **Gene Silencing:**
- **Translation Inhibition:** The degradation of the target mRNA effectively silences the gene by preventing the production of the corresponding protein.
- **Amplification and Spread:** The siRNA can trigger a cascade of events, leading to the production of more siRNAs and silencing of additional target mRNAs. This amplification mechanism contributes to the potent and widespread effects of RNAi.

In summary, siRNA processing is a complex and tightly regulated process that plays a crucial role in gene silencing. It involves the generation of siRNAs from dsRNA, the assembly of RISC, and the targeted degradation of mRNA. This pathway has significant implications for understanding gene regulation, developing new therapeutic strategies, and exploring the mechanisms of disease.
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Proteins (4)

Compounds (35)