RNA-induced silencing complex
Encyclopedia
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.
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-miRNA
s, 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.
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.
Small interfering RNA
Small interfering RNA , sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 nucleotides in length, that play a variety of roles in biology. The most notable role of siRNA is its involvement in the RNA interference pathway, where it...
(siRNA) or micro RNA
Micro RNA
A microRNA is a short ribonucleic acid molecule found in eukaryotic cells. A microRNA molecule has very few nucleotides compared with other RNAs....
(miRNA). RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
. 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 endonucleaseEndonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...
Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...
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-miRNA
Mirna
Mirna may refer to:geographical entities* Mirna , a river in Istria, Croatia* Mirna , a river in Slovenia, tributary of the river Sava* Mirna , a settlement in the municipality of Mirna in Southeastern Sloveniapeople...
s, cleaves a pre-miRNA stem-loop or a dsRNA, a 20- to 25-base-pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a 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 argonauteArgonauteArgonaute proteins are the catalytic components of the RNA-induced silencing complex , the protein complex responsible for the gene silencing phenomenon known as RNA interference . Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs , small interfering RNAs and...
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 with a bound siRNA recognizes complementaryComplementarity (molecular biology)
In molecular biology, complementarity is a property of double-stranded nucleic acids such as DNA, as well as DNA:RNA duplexes. Each strand is complementary to the other in that the base pairs between them are non-covalently connected via two or three hydrogen bonds...
messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
(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
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
.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.