Small interfering RNA

Small interfering RNA ( siRNA short ) are short, single-stranded or double-stranded ribonucleic acid molecules. You not encode a protein but play particularly in the context of RNA interference in the cells of living organisms with a nucleus ( eukaryotes ) play an important role in the defense against viruses and in regulating the expression of genes.

Structure

An siRNA is about 19 ​​to 23 base pairs long double-stranded RNA, single-stranded overhangs of which are each at the 3 ' end by two nucleotides. The 5 'end of each strand is phosphorylated, while the 3'- ends carry free hydroxyl groups.

Biosynthesis

The siRNA is formed by a division of a large double-stranded RNA molecule. This precursor RNA can be several hundreds to thousands of base pairs in size and falls for example, at the time of duplication of viral RNA. At the division in particular the enzyme Dicer, an RNase called is of type III, involved.

Function

The siRNA is formed in many cells as a result of infection with an RNA virus and in the defense against foreign RNA plays in particular in plants play an important role. It is produced as a fission product in the duplication ( replication ) of the viral RNA and also serves the cell to recognize and destroy these foreign RNA. Similar mechanisms could also be found in fungi, nematodes and insects. Many viruses attempt in turn to escape this defense mechanism via inhibition of proteins involved in RNA interference.

Also in gene regulation via the Posttranscriptional gene silencing, the siRNA play a central role in determining the selectivity. Along with specific protein components to form the RNA-induced silencing complex (RISC). Only one strand of the siRNA, which is called in this connection, leading strand " is adopted here. Single-stranded RNA, particularly messenger RNA, that is, containing the leading strand of the siRNA complementary to the nucleotide sequence, is destroyed by the RISC or preventing protein translation in other ways. Since only those mRNA is translated to protein, which escapes the RISC, the activity of the affected gene is reduced. The first victim is likely to be generally the partial strand not incorporated the siRNA.

Application

SiRNA is used in particular in basic research to elucidate the still unknown function of a gene known to be examined and its encoded protein using RNA interference. Shutdown of the gene by the targeted using siRNA, the function of the encoded protein can be derived from it. Also for the inverted question, the search for those responsible for a known function or a particular characteristic genes or proteins, siRNA libraries can be used.

The therapeutic use of siRNA in medicine is the subject of research. Some potential siRNA -based drugs are in late stages of clinical testing. After the failure of several large pharmaceutical companies Bevasiranib presented, including Hoffmann -La Roche, one of their siRNA -based development programs.