RNA-induced silencing complex

RNA-Induced Silencing Complex, or RISC, is a multiprotein complex that incorporates one strand of a small interfering RNA (siRNA) or micro RNA (miRNA). RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA. When it finds a complementary strand, it activates RNase and cleaves the RNA. This process is important both in gene regulation by microRNAs and in defense against viral infections, which often use double-stranded RNA as an infectious vector.

Strands
The RNA endonuclease Dicer plays a role in aiding RISC action by providing the initial RNA material to activate the complex as well as the first RNA substrate molecule. When the Dicer, which has endonuclease activity against dsRNA and pre-miRNAs, cleaves a pre-miRNA stem-loop or a dsRNA, a 20- to 25-base-pair double-stranded RNA fragment is formed with a two-nucleotide 3' overhang at each end.


 * One strand is integrated into the RISC complex. This strand is known as the guide strand and is selected by the argonaute protein, the catalytically active RNase in the RISC complex, on the basis of the thermodynamic stability of the 5' end. The strand with a less thermodynamically stable 5' end is loaded into the RISC complex.


 * The remaining strand, known as the anti-guide or passenger strand, is degraded as a RISC complex substrate.

Binding
The RISC complex with a bound siRNA recognizes complementary messenger RNA (mRNA) molecules and degrades them, resulting in substantially decreased levels of protein translation and effectively turning off the gene. It is as yet unclear how the activated RISC complex locates the mRNA targets in the cell, though it has been shown that the process can occur in situations outside of ongoing protein translation from mRNA. Endogenously expressed miRNA in metazoans is usually imperfectly complementary to a large number of nuclear genes and has a modulating effect on these genes' levels of expression via translational repression. However, in plants the process has a much greater specificity to the mRNA and usually each miRNA only binds to one mRNA. Recently identified members of RISC complex are SND1(p100 Coactivator or Tudor SN)and AEG-1(MTDH). AEG-1 and SND1 are oncogenes and regulates various gene expression.