Small interfering RNA (siRNA)

Article By:

Price, David H. Department of Biochemistry, University of Iowa, Iowa City, Iowa.

Last reviewed:June 2020

DOI:https://doi.org/10.1036/1097-8542.800930

Short, double-stranded ribonucleic acid (RNA) molecules that interface with cellular machinery and lead to downregulation of the expression of specific eukaryotic genes in a process called RNA interference (RNAi). Few discoveries have created as much excitement to the basic and medical research community as the finding that small, double-stranded RNAs regulate gene expression. Some of the first indications of the RNAi process were found in plants. When a copy of a plant gene that is responsible for dark-colored flowers was artificially introduced into petunias, an unexpected result occurred. Some of the plants that had colored flowers now produced white flowers. The added gene was not expressed well and actually caused reduction in the expression of the endogenous gene in a process called cosuppression. Related results were found by plant virologists studying how plants protect themselves from viral infections. The plant scientists found that specific messenger RNAs (mRNAs) that encoded plant or viral proteins were being degraded, but the mechanism was elusive. The seminal observation that double-stranded RNA (dsRNA) was capable of silencing genes was reported by Andrew Fire and Craig Mello in 1998. They shared the Nobel Prize in Physiology or Medicine only 8 years later. Since the initial discovery, it has become clear that small interfering RNAs (siRNAs) play a large role in controlling gene expression in a diverse array of organisms, including yeast, worms, flies, and mammals. Perhaps more importantly, the knowledge has spawned practical applications that have revolutionized molecular biology. See also: Gene; Molecular biology; Ribonucleic acid (RNA)

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