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Small interfering RNA (siRNA) are small pieces of double-stranded (ds) RNA, usually about 21 nucleotides long, with 3' overhangs (2 nucleotides) at each end that can be used to "interfere" with the translation of proteins by binding to and promoting the degradation of messenger RNA (mRNA) at specific sequences. In doing so, they prevent the production of specific proteins based on the nucleotide sequences of their corresponding mRNA. The process is called RNA interference (RNAi), and may also be referred to as siRNA silencing or siRNA knockdown.

siRNA are generally considered to have come from longer strands of exogenous RNA which is taken up by the cell and undergoes further processing. The RNA often comes from vectors, like viruses or transposons, and have been found to play a role in antiviral defense, degradation of over-produced mRNA or mRNA for which translation has been aborted, and preventing disruption of genomic DNA by transposons.

Each siRNA strand has a 5' phosphate group and a 3' hydroxyl (OH) group. They are produced from dsRNA or hairpin looped RNA which, after entering a cell is cleaved by an RNase III–like enzyme, called Dicer, using RNase or restriction enzymes. The siRNA are then incorporated into a multi-subunit protein complex called RNAi induced silencing complex (RISC). RISC "seeks out" an appropriate target mRNA, where the siRNA then unwinds and, it is believed, the antisense strand directs degradation of the complimentary strand of mRNA, using a combination of endo- and exonuclease enzymes.

Many diseases can potentially be treated by inhibiting gene expression. Therefore, the design of synthetic siRNA for therapeutic uses has become a popular objective of many biopharmaceutical companies.


Tsai, C.S. Biomacromolecules: Introduction to structure, function and informatics. Wiley-Liss, 2007.

Also Known As: small interfering RNA

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