Friday, 12 July 2013

siRNA

Small interfering RNA (siRNA)  known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 nucleotides in length, that play numerous roles in biology.
 The most memorable role of siRNA is its participation in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene. In addition to its role in the RNAi pathway, it also acts in RNAi-related pathways, as an antiviral mechanism or in shaping the chromatin structure of a genome.

siRNAs were discovered by David Baulcombe's group at the Sainsbury Laboratory in Norwich, England, as part of post-transcriptional gene silencing (PTGS) in plants.
In 2001,Shortly thereafter synthetic siRNAs were shown to be able to induce RNAi in mammalian cells by Thomas Tuschl, and colleagues in a paper published in Nature.


the structure

Each strand of siRNA has a 5' phosphate group and a 3' hydroxyl (-OH) group.  This structure is the result of processing by dicer, which converts either long dsRNAs or small hairpin RNAs into siRNAs. As well siRNAs can be introduced into cells by transfection methods to cause the specific knockdown of a gene of interest.  In extract, any gene whose sequence is known can, thus, be targeted based on sequence complementarity with an appropriately tailored siRNA.
So siRNAs are considered an important tool for gene control and drug target validation studies in the post-genomic era.


Gene silencing process by RNAi is controlled by the RNA-induced silencing complex (RISC) and is initiated by short double-stranded RNA molecules in a cell's cytoplasm, where they interact with the catalytic RISC component argonaute When the dsRNA is exogenous (coming from infection by a virus with an RNA genome or laboratory manipulations), the RNA is imported directly into the cytoplasm and cleaved to short fragments by the enzyme. The initiating dsRNA can also be endogenous (originating in the cell), as in pre-microRNAs expressed from RNA-coding genes in the genome. The primary transcripts from such genes are first processed to form the characteristic stem-loop structure of pre-miRNA in the nucleus, then exported to the cytoplasm to be cleaved by Dicer. Thus, the two dsRNA pathways, exogenous and endogenous, converge at the RISC complex.
http://www.abcam.com/ps/CMS/Images/siRNA.jpg

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