Small interfering RNA (siRNA)

Developers

D. Baulcombe, T. Tuschl, C. Mello, A. Fire, P. D. Zamore, L. C. Li etc.

Description of the technology

Small interfering RNAs (siRNA) are short (usually 21-nucleotide long) double-stranded RNAs with two unpaired prominent nucleotides at the 3'-ends. Interaction of small interfering RNAs with mRNA of a target gene leads to degradation of the latter (during the process known as RNA interference). That prevents translation of mRNA to a protein encoded on the ribosomes. Finally, the result of action of small interfering RNAs is the same as if gene expression barely went down.

Small interfering RNAs were discovered in 1999 by D. Baulcombe’s team (Great Britain) as a component of the system of post-transcriptional gene silencing in plants. In 2001, T. Tuschl’s team showed that small interfering RNAs could induce RNA interference in the cells of mammals.

Practical application

Small interfering RNAs can be used for biomedical studies and drug development.
Small interfering RNAs can be artificially introduced into cells in order to knock down a certain gene or genes. In such a way, expression of almost any gene can be changed intentionally. Thanks to this property, small interfering RNAs are very suitable instrument in studies on gene functions and drug targets. Since pathogenesis of diseases is also stipulated by gene activity, it is supposed that in some cases, knock down of a gene using small interfering RNAs can give a therapeutic effect.

However, the use of RNA interference, which is based on the small interfering RNAs, in animals and, particularly, in humans is a matter of some difficulty. It was shown in the experiments that effectiveness of small interfering RNAs varies in different types of cells: some cells respond to the impact of small interfering RNAs easily and demonstrate decrease in gene expression, while other ones do not show such effects in spite of effective transfection. Reasons of that phenomenon are poorly understood yet.

Laboratories

• Phil Zamore’s Lab, University of Massachusetts Medical School, Worcester, Massachusetts (USA)
• Howard Hughes Medical Institute, Laboratory of RNA Molecular Biology, New York (USA)
• Institute of Molecular Biology, Mainz (Germany)

Links

Publications

• Hamilton, Andrew J., and David C. Baulcombe. «A species of small antisense RNA in posttranscriptional gene silencing in plants." Science 286.5441 (1999): 950–952.
• Elbashir, Sayda M., et al. «Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells." nature 411.6836 (2001): 494–498.
• Alekseev, Oleg M., et al. «Analysis of gene expression profiles in HeLa cells in response to overexpression or siRNA-mediated depletion of NASP." Reprod Biol Endocrinol 7.45 (2009): 1–17.
• Li, Long-Cheng. «Small RNA-mediated gene activation 13." RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity (2008): 189.
• Галицкий, В. А. «Гипотеза о механизме инициации малыми РНК метилирования ДНК de novo и аллельного исключения." Цитология 50.4 (2008): 277–286.