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Researchers solve piece of large-scale gene silencing mystery
Date:12/4/2008

A team led by Craig Pikaard, Ph.D., WUSTL professor of biology in Arts & Sciences, has made a breakthrough in understanding the phenomenon of nucleolar dominance, the silencing of an entire parental set of ribosomal RNA genes in a hybrid plant or animal.

Since the machinery involved in nucleolar dominance is some of the same machinery that can go haywire in diseases such as cancer, Pikaard and his collaborators' research may have important implications for applied medical research.

Nucleolar dominance occurs when nucleoli, protein-rich, dense regions of RNA within the nucleus, form on the chromosomes inherited from one parent, but not on the chromosomes inherited from the other parent. Expression of ribosomal RNA genes drives the formation of these nucleoli. The hybrid, a result of a cross-breeding of two different species, always "chooses" to express the ribosomal RNA genes of one particular parental species, regardless of whether that species happens to be the maternal or paternal parent.

Ribosomal RNAs, or rRNAs, are a major component of the ribosomes, the protein manufacturers of the cell. Because rRNA genes are highly redundant, cells use nucleolar dominance to control the dosage of ribosomes in an organism.

According to Pikaard, if researchers could harness the silencing machinery involved in nucleolar dominance to limit the expression of rRNA genes, they could potentially slow the growth rate of tumor cells and thereby slow the progression of diseases like cancer.

In cancer cells, nucleoli are conspicuously large because of a dramatic increase in the transcription of rRNAs, which in turn leads to an increase in the production of ribosomes. This escalation in ribosome activity means that the cell can synthesize proteins at an alarmingly rapid rate, which contributes to the out-of-control cell proliferation that is the disease's trademark.

Completely silencing all ribosomal genes would not be a
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Contact: Craig Pikaard
pikaard@wustl.edu
314-935-7569
Washington University in St. Louis
Source:Eurekalert

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