RNA Interference

Investigation of the mechanism of action of antisense RNA led to the surprising discovery that naturally occurring double-stranded RNA molecules (dsRNA) suppress gene expression as well as or better than antisense sequences. This suppression by dsRNA of expression of the related gene is called RNA interference. dsRNA molecules are cut into short segments by nucleases; the antisense strand of such a segment then peels off and binds with its complementary mRNA. This new, double-stranded RNA is then subject to further nuclease attack. RNA interference is believed to be an ancient means of protecting against double-stranded RNA viruses. Further understanding of RNA interference may lead to improvements in or replacement of antisense therapies. see also Gene Therapy; Nucleases; Nucleotide; RNA Interference; Transgenic Plants.

Richard Robinson

Bibliography

Smith C. J. S., et al. "Antisense RNA Inhibition of Polygalacturonase Gene Expression in Transgenic Tomatoes." Nature 334 (1988): 724-726.

Tamm I., B. Dorken, and G. Hartmann. "Antisense Therapy in Oncology: New Hope for an Old Idea?" Lancet 358, no. 9280 (2001): 489-497.

Internet Resource

"Antisense DNA." Michigan State University. <http://www.cem.msu.edu/~cem181h/ projects/97/antisense/dia1.gif>.

Apoptosis from injury or disease

Death is an inevitable fact of life for organisms. Increasingly, biologists have come to realize that death is also, in many cases, an important and predestined fate of individual cells of organisms. Apoptosis is a process by which cells in a multicellular organism commit suicide. While cells can die as a result of necrosis, apoptosis is a form of death that the cell itself initiates, necrosis cell death regulates, and executes using an elaborate arsenal of cellular and molecular machinery. For this reason, the term apoptosis is often used interchangeably with the term "programmed cell death," or PCD (although technically, apoptosis is but one particular form of programmed cell death). There is some disagreement on the origins of the word. The word apoptosis has ancient Greek origins, referring to the falling of leaves, or possibly "dropping of scabs" or "falling off of bones." There is even less agreement on its proper pronunciation, and even specialists in the field seem to use every possible way to say the word. "A-pop-TOE-sis" and "AP-oh-TOE-sis" are both common.

Magnification (6000X) of apoptosis, or cell death. Programmed cell death in the human body allows, among other things, for young children's brains to develop and for a female's monthly menstruation to occur.

APOPTOSIS GENES IN C. ELEGANS

Much of our understanding of what causes apoptosis comes from genetic studies in Caenorhabditis elegans. Several cell death proteins (CED) proteins were identified in C. elegans by studying apoptosis-defective mutants. The main executioner is CED-3, a caspase, which becomes activated by CED-4, another caspase. The central guardian protecting cells against apoptosis is CED-9, which inhibits the actions of CED-4 and CED-3. CED-9 has a mammalian homolog, called BCL-2, which serves a similar role in mammals.

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