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The Human Genome

Gene Silencing

There exists an unexplained but potentially powerful phenomenon of posttranscriptional gene silencing called RNA interference. Observations have now verified that if a piece of double-stranded RNA (dsRNA) is introduced into the brain or even into the peritoneal cavity of an animal, then the destruction of the homolog of that dsRNA in the brain cell occurs. The figure shows the expression of the ß-galactosidase gene without (A and B) and with (C and D) RNA interference in the optic lobe and in the antennal lobe of an adult drosophila. These images illustrate that the RNA interference not only reduces the tissue levels of RNA but also alters the individual phenotype of the organism. The mechanism of this stable epigenetic modification is not fully understood. The speculation about the mechanism is that sequence-specific RNA degradation is accomplished by the action of an endogenous ribonuclease that reduces dsRNA to small (21–23 base pairs) interfering dsRNAs, thus producing mediators of the RNA interference effect. The overall purpose of this gene-silencing mechanism is also a matter of speculation: it might be a protective mechanism important to a cell in its fight against foreign RNA from viruses. A better understanding of the full mechanism of RNA interference is necessary to speculate more fully on its applications. However, one can imagine that a technique of this type would be a valuable tool for studying loss-of-function phenotypes in functional genomics—for characterizing the role of specific gene involvement in the development and function of an adult CNS for example. Possibly, RNA interference could be developed for therapeutic gene silencing as well.

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The figure shows the expression of the ß-galactosidase gene (lacZ) in the optic lobe (A) and in the antennal lobe (B) of an adult drosophila. When that drosophila is injected with a sequence of double-stranded RNA matched to the product of ß-galactosidase gene (lacZ> RNA), then the expression of the ß-galactosidase gene in the optic lobe (C) and antennal lobe (D) is profoundly inhibited.

Footnotes

Address reprint requests to Dr. Tamminga, Maryland Psychiatric Research Center, University of Maryland, P.O. Box 21247, Baltimore, MD 21228; ctamming{at}mprc.umaryland.edu (e-mail). Image courtesy of the authors.

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Manev, H. Articles by Dimitrijevic, N. Search for Related Content PubMed Citation Articles by Manev, H. Articles by Dimitrijevic, N. Genetics

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