RNA interference abbr., RNAi (rus. РНК-интерференция) — Biological mechanism to control gene activity through short double-stranded RNAs and special protein complexes which results in selective degradation of certain mRNAs or inhibition of translation of many mRNAs in a cell.

Description

The RNA-interference mechanism consists of cleaving a double-stranded RNA present in a cell, which often represents a foreign genome of RNA viruses, into short fragments with Dicer enzyme. One of the two strands of an RNA fragment is integrated into the RISC protein complex (RNA-induced silencing complex) and interacts with a complementary viral mRNA, which then is cleaved with the RISC complex. This stops the synthesis of the protein encoded by this mRNA . Along with response to foreign RNA, cells synthesise their own short interfering RNAs (siRNA) from the so-called microRNA (miRNA). MicroRNA processing is similar to processing of double-stranded viral RNAs. MicroRNAs inhibit cell protein synthesis through degrading mRNAs or building on mRNAs barriers for protein-synthesizing molecular machine (ribosomes). Thus, microRNAs are part of the system for regulating gene expression in a cell.

U.S. scientists Andrew Fire and Craig Mello were awarded the Nobel Prize in Physiology or Medicine in 2006 for discovery of RNA interference. On the basis of the described mechanism, methods have been developed to suppress gene expression by short synthetic RNA duplexes. Such duplexes can be created against any mRNA because the genome sequences of many organisms, including humans, are already known. Now the use of RNA interference to treat infectious, oncological and other diseases is under active development.

Nanobiotechnology is widely used for the delivery of synthetic RNA duplexes to cells including liposomes, carbon nanotubes, self-assembling cyclodextrin-based polymer nanoparticles, etc. The surface of these nanoparticles is modified with antibodies and other vectors to ensure targeted delivery to cancer cells, intravascular lesions, etc.

Illustrations

Dicer fragment cuts the two-strand RNA, resulting in a siRNA. These processed RNAs combine with c

Dicer fragment cuts the two-strand RNA, resulting in a siRNA. These processed RNAs combine with catalytically active proteins (nucleases, RISC). A combination of RISC and siRNA specifically decomposes mRNA and prevents translation.


Author

  • Shirinsky Vladimir P.

Sources

  1. Fire A., Xu S., Montgomery M., Kostas S. et al. Potent and specific genetic interference by doublestranded RNA in Caenorhabditis elegans // Nature. 1998. V. 391, №6669. P. 806–811.
  2. Matzke M. A., Matzke A. J.M. Planting the Seeds of a New Paradigm // PLoS Biol. 2004. V. 2, №5. e133.

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