by Subhankar Chakraborty

Created on: December 12, 2006   Last Updated: May 02, 2007

RNA interference

RNA interference is the phenomenon wherein a double stranded RNA (ds RNA) molecule with two overhanging nucleotides (usually TT or UU) at its 3' end (called a "short interfering RNA" or siRNA) silences the expression of a gene at the post-transcription level. siRNA molecules need to be differentiated from antisense RNA, which is a piece of DNA complementary to a specific mRNA sequence that when introduced into the cell, binds to its complementary mRNA and thus blocks translation. dsRNA molecules are usually introduced into the cell through a viral genome (as during viral infections). They silence expression of a gene by the following mechanism

- The ds RNA upon entering into the cell are processed by a protein called DICER. DICER cuts the ds RNA into smaller double stranded fragments with a two nucleotide overhang at each 3' end (now called siRNA). This siRNA now unwinds and binds with very high specificity to a complementary sequence on the mRNA. It then recruits a multiprotein complex called RISC (RNA induced silencing complex), which includes an RNAse that is an endonuclease and cleaves the mRNA in the center of the portion that is bound to the siRNA. The cleaved mRNA is now useless and floats freely in the cell. The cell recognizes any free floating nucleic acid as being foreign and degrades these mRNA fragments (by exonucleases) thereby silencing the expression of the protein encoded by its mRNA.
- Alternately, RISC may bind to the siRNA bound to the 3'untranslated region of the mRNA and blocks the movement of ribosome along it, thereby blocking translation.

Role of RNA interference in a normal cell

The present view is that RNA interference is an evolutionarily conserved mechanism which cells have evolved to tackle invasion by essentially viruses since many viruses have RNA as their genetic material. In support of this, the protein complex RISC functions to identify mRNA sequences that have been cleaved by dicer and proceeds to degrade all mRNAs bearing the same sequence in the cell. It is proposed that RNA interference could also be used by the cell to prevent the movement of highly mobile genetic elements, called transposons and also of repetitive elements. Further, it could be used to control temporal expression of genes, especially during development.
Initial experiments on RNA interference were conducted in invertebrates including nematodes and fruit flies. In case of mammals however only a ds RNA less than 30 nucleotides can silence selectively

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