Schematic Overview of the RNAi Mechanism
The presence of double-stranded RNA (dsRNA) triggers the
posttranscriptional silencing of the gene which is targeted by the
dsRNA. Different RNA molecules can induce gene silencing:
- siRNAs, which are delivered into the cell or
- shRNAs, which are transcribed from a plasmid.
Although the origin and the structure of the RNA molecules
differ, they share the subsequent mode of action. The common entry
point for gene silencing is the formation of the RNA-induced
silencing complex (RISC) from 5'-phosphorylated siRNAs and
endogenous Argonaute protein. shRNAs require cleavage by the
endogenous cytoplasmic nuclease Dicer to yield siRNAs which are 21
to 27 nucleotides long.
The Argonaute protein and one strand of the siRNA form the
RNA-induced silencing complex (RISC). The incorporated RNA strand
determines the sequence-specificity of the gene silencing. RISC
binds to the mRNA which is targeted by the single RNA strand within
the complex and cleaves the mRNA. The cleaved mRNA cannot be
translated. RISC dissociates and can cleave other mRNAs. By that
even a few numbers of the RNA-induced silencing complex can lead to
high-level gene silencing.
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