Silent Sites Speak

Silent Sites Speak


August 9, 2001

I do set My bow in the cloud

It was recently found (CNN.com/HEALTH, Gene Causes Type of Muscular Dystrophy, August 3, 2001) that a type of muscular dystrophy is caused by a novel genetic mechanism. A mutation in a gene on chromosome 3 causes the messenger RNA to become harmful to the cell:

Writing in the journal Science, they said the disease was the first for which there was indisputable evidence that it was triggered by defective RNA, a messenger molecule that normally serves merely to translate the DNA code into proteins.

...

"In the past, it was so unclear what was causing it that it was impossible to come up with any concept or approach to treating it. At least now we know what the mechanism of the disease is. It's a really novel mechanism," Day said.

In an interview, Ranum noted that the gene that causes the other type of myotonic dystrophy was located in 1992. She said the new research suggested that RNA was responsible for both types of the disease.

Ranum said in the past researchers had focused on protein abnormalities as the cause of genetic disorders, believing RNA had little or no direct role in causing disease.

Sharon Hesterlee, director of research development for the Muscular Dystrophy Association, said understanding RNA's involvement "helps direct our therapeutic efforts." Hesterlee's group helped fund the research.

"What we have to do is get rid of this poisonous RNA. And there may be some options for doing that," Hesterlee added.

The messenger RNA is used to translate DNA into protein. RNA polymerase reads genes from the DNA and translates them into messenger RNA. The messenger RNA is then transported out of the nucleus into the ribosomes where it used to construct proteins according to the information given in the genes. The proteins must then fold into the proper 3 dimensional structure in order to become useful to the cell. "Chaperones" are proteins that help proteins to fold properly. Actually, many proteins do not fold properly and must be removed from the cell. If there are too many misfolded proteins in the cell it becomes impossible for the cell to remove them all and they stick together in bunches, leading to some pathological conditions (see Science Vol. 292, 25 May 2001, pp. 1467-8, "Protein Clumps Hijack Cell's Clearance System.")

It had been thought that the messenger RNA did not have chemical activity in the cell. However, RNA itself folds into complex three dimensional shapes, unlike DNA, and can have chemical activity in a variety of ways. In fact, scientists (Science, 18 May, 2001, page 1278, "Making Copies in the RNA World") have created an RNA enzyme that can make copies of other RNA molecules of bounded length. Scientists believe that this supports the "RNA world" scenario, in which the first reproducing life forms were composed of RNA.

The new research mentioned above shows that even messenger RNA can be harmful to the cell because of its chemical properties. This is significant because even the "silent sites" of DNA influence the messenger RNA. The silent sites do not influence the protein constructed from a gene, and so they are thought to have little function in many cases. However, the fact that messenger RNA can have a chemical effect on the cell shows that even the silent sites can make a difference.

It is not only in their effect on the messenger RNA that silent sites can affect the cell. The DNA itself has chemical activity, and a number of proteins bind to specific sites on the DNA depending on its code; these include genetic promoters and repressers and the RNA polymerase itself.

This is significant because it can explain why the silent sites are similar in similar organisms, even if they do not have a common ancestor. The silent sites may be similar because they have a similar effect on the messenger RNA and on the activity of the DNA. Biologists argue that the similarity in the silent sites between humans and apes proves that they evolved from a common ancestor, because the silent sites have little function. However, these sites, as has been shown, have many functions and would be expected to be similar in similar organisms, regardless of common descent.


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