Small interfering RNA

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Structure of the siRNA

Small interfering RNA , abbreviated as siRNA , (Eng. For small intervening RNA ) are short, single or double stranded ribonucleic acid - molecules 20 to 25 base pairs in length. They do not code for proteins , but rather combine with complementary single-stranded ribonucleic acid molecules, thereby preventing their normal function.

This process is called RNA interference and plays an important role in the cells of living things with a nucleus , the eukaryotes . RNA interference suppresses the expression of genes and stops viruses from replicating .

structure

An siRNA is an approximately 19 to 23 base pair long RNA double strand, the single strands of which overhang by two nucleotides at the 3 'end. The 5 'end of each strand is phosphorylated , while the 3' ends carry free hydroxyl groups .

biosynthesis

The siRNA is formed by cleaving a large double-stranded RNA molecule. This precursor RNA can be several hundreds to thousands of base pairs in size and is obtained, for example, from the replication of viral RNA. The enzyme Dicer , a so-called RNase of type III, is particularly involved in the cleavage .

function

Cellular function of siRNA in RNA interference

The siRNA is formed in many cells as a result of infection with an RNA virus and plays an important role in the defense against foreign RNA, especially in plants. It occurs as a cleavage product during the duplication ( replication ) of the virus RNA and at the same time serves the cell to recognize and destroy this foreign RNA. Similar mechanisms have also been found in fungi, roundworms and insects. Numerous viruses try for their part to evade this defense mechanism by inhibiting the proteins involved in the RNA interference.

The siRNA can also play a central role in gene regulation via post-transcriptional gene silencing , as it determines the selectivity. Together with special protein components, it forms the RNA-induced silencing complex (RISC). Only one strand of the siRNA, which is called the 'leading strand' in this context, is taken over. Single-stranded RNA, in particular messenger RNA , which contains the nucleotide sequence complementary to the leading strand of the siRNA, is destroyed by the RISC or the translation to protein is prevented in some other way. Since only the mRNA that escapes the RISC is translated to the protein, the activity of the affected gene is reduced. In general, the first victim is likely to be the partial strand of the siRNA that has not been adopted.

application

Bevasiranib

siRNA is used especially in basic research to elucidate the still unknown function of a known gene to be examined and its encoded protein with the help of RNA interference. By specifically switching off the gene with the help of siRNA, the function of the protein it encodes can be derived. SiRNA libraries can also be used for the opposite question, the search for the genes or proteins responsible for a known function or a certain characteristic.

The therapeutic application of siRNA in medicine is also the subject of research. Some siRNA-based potential drugs are being tested. For example, some drugs that are effective against filoviruses in monkeys , such as Marburg and Ebola viruses, are based on siRNA.

After the failure of Bevasiranib , several large pharmaceutical companies, including Hoffmann-La Roche, discontinued their siRNA-based development programs.

literature

  • H. Siomi, MC Siomi: On the road to reading the RNA interference code . In: Nature . tape 457 , no. 7228 , January 2009, p. 396-404 , doi : 10.1038 / nature07754 , PMID 19158785 .
  • M. Jinek , JA Doudna : A three-dimensional view of the molecular machinery of RNA interference . In: Nature . tape 457 , no. 7228 , January 2009, p. 405-412 , doi : 10.1038 / nature07755 , PMID 19158786 .
  • SM Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, T. Tuschl: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells . In: Nature . tape 411 , 2001, pp. 494-498 , PMID 11373684 .

Individual evidence

  1. ↑ J. Haasnoot, EM Westerhout, B. Berkhout: RNA interference against viruses: strike and counterstrike . In: Nat. Biotechnol. tape 25 , no. December 12 , 2007, pp. 1435-1443 , doi : 10.1038 / nbt1369 , PMID 18066040 .
  2. ↑ Julia Merlot: Related to Ebola: New drug protects monkeys from Marburg fever. In: Spiegel online. August 20, 2014, accessed August 20, 2014 .
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