siRNA-mediated gene silencing by mRNA destabilization

Definition

Target type: biologicalprocess

An siRNA-mediated post-transcriptional gene silencing pathway in which small interfering RNAs (siRNAs) direct the cleavage of target mRNAs. Once incorporated into a RNA-induced silencing complex (RISC), an siRNA will typically direct cleavage by base pairing with perfect or near-perfect complementarity to the target mRNA. [GOC:BHF, GOC:BHF_miRNA, GOC:rph, PMID:15260970]

siRNA-mediated gene silencing through mRNA destabilization is a powerful and widely used technique in molecular biology. The process begins with the introduction of small interfering RNA (siRNA) molecules, which are double-stranded RNA molecules typically 21 nucleotides in length. These siRNAs are designed to target specific mRNA sequences.

Once inside the cell, the siRNA molecules are recognized by the RNA-induced silencing complex (RISC). RISC is a multi-protein complex that unwinds the siRNA duplex, leaving the guide strand to bind to the target mRNA. This guide strand acts as a template for the RISC complex to recognize and bind to complementary sequences within the target mRNA.

Once bound, the RISC complex initiates mRNA destabilization through a series of mechanisms. One primary mechanism involves the recruitment of a protein called decapping enzyme. Decapping enzyme removes the 5' cap from the mRNA molecule, which is essential for its stability and translation. Without the 5' cap, the mRNA becomes vulnerable to degradation by exonucleases, which chew away at the mRNA from the 5' end.

Another important mechanism involves the recruitment of exonucleases that degrade the mRNA from the 3' end. These exonucleases can enter the mRNA molecule through the poly(A) tail, a string of adenine nucleotides at the 3' end that helps stabilize the mRNA. By degrading the poly(A) tail, these exonucleases further destabilize the mRNA and make it susceptible to degradation by other enzymes.

Furthermore, RISC-mediated mRNA destabilization can involve the activation of endonucleases, which can cleave the mRNA molecule at specific sites. These cleavage events further contribute to the degradation of the target mRNA.

Overall, siRNA-mediated gene silencing through mRNA destabilization involves a complex series of events orchestrated by the RISC complex. By targeting specific mRNA sequences, siRNAs can trigger the removal of the 5' cap, degradation of the poly(A) tail, and activation of endonucleases, ultimately leading to the rapid and efficient degradation of the target mRNA. This reduction in target mRNA levels effectively silences gene expression, providing a powerful tool for studying gene function and for developing therapeutic strategies.'
"

Proteins (1)

Compounds (4)