page_title: Small interfering RNA
section_title: Mechanism
hierarchical_section_title: Small interfering RNA / Mechanism
caption_attribution_description: English: siRNA mechanism
context_page_description: Small interfering RNA, sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA non-coding RNA molecules, typically 20-27 base pairs in length, similar to miRNA, and operating within the RNA interference pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, preventing translation.
context_section_description: The mechanism by which natural siRNA causes gene silencing through repression of translation occurs as follows:
  Long dsRNA (which can come from hairpin, complementary RNAs, and RNA-dependent RNA polymerases) is cleaved by an endo-ribonuclease called Dicer. Dicer cuts the long dsRNA to form short interfering RNA or siRNA; this is what enables the molecules to form the RNA-Induced Silencing Complex (RISC).
  Once siRNA enters the cell it gets incorporated into other proteins to form the RISC.
  Once the siRNA is part of the RISC complex, the siRNA is unwound to form single stranded siRNA.
  The strand that is thermodynamically less stable due to its base pairing at the 5´end is chosen to remain part of the RISC-complex
  The single stranded siRNA which is part of the RISC complex now can scan and find a complementary mRNA
  Once the single stranded siRNA (part of the RISC complex) binds to its target mRNA, it induces mRNA cleavage.
  The mRNA is now cut and recognized as abnormal by the cell. This causes degradation of the mRNA and in turn no translation of the mRNA into amino acids and then proteins. Thus silencing the gene that encodes that mRNA.
  siRNA is also similar to miRNA, however, miRNAs are derived from shorter stemloop RNA products, typically silence genes by repression of translation, and have broader specificity of action, while siRNAs typically work by cleaving the mRNA before translation, and have 100% complementarity, thus very tight target specificity.
caption: siRNA Mechanism
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