Ribozymes: molecular scissors for investigating genetic function

Ribozymes are molecular scissors that cut RNA, the molecular messages given by genes in order to produce proteins. These molecular scissors provide a very useful means of studying gene function since by cutting the RNA with a ribozyme a gene can be effectively turned off. Such a turning off of the gene can then be studied in terms of what happens to the cell structure in the cell in which the gene has been turned off and in terms of what happens to the molecular soup within the cell itself.

Perhaps the earliest report of these ribozymes or catalytic RNAs as they were first known came from Cech in 1987 in a paper published in NATURE. This was seen as a major discovery since until then proteins were thought to be the only entity capable of behaving as enzymes. A number of labs around the world are now using these ribozymes to study gene function in precisely the manner described above most notably in the study of HIV, the AIDS virus, and in Cancer research. Mang Yu and coworkers at the University of California recently managed to show just how effective HIV-directed ribozymes can be since they used ribozymes to provide white blood cells with resistance to HIV infection.

However, using ribozymes as molecular scissors is not as easy as it sounds. The biggest problem is that the cell is producing a large number of RNAs from a huge number of different genes. Obviously when the ribozyme is introduced into the cell, the researcher does not want the ribozyme to cut all the RNA messengers since a large number of genes will be turned off. This problem of specificity is something that has to be considered very carefully prior to introducing the ribozyme into the cell otherwise anything that then happens in the cell will be too difficult to interpret.

Mode of Action of a Ribozyme - the Molecular Scissors
Our laboratory in Strasbourg is currently making use of ribozymes to study the involvement of certain gene sequences in the onset of Spinal Muscular Atrophy a disorder that can lead to severe degeneration of both muscle and nerve cells in the affected individual. By designing ribozymes that target the RNA messenger of certain genetic sequences in muscle cells that have been cultured under special conditions, it is hoped that changes in these cultured cells will be observed that resemble the changes that are seen in Spinal Muscular Atrophy patients. This will not only lead to a larger understanding of exactly what role such genetic sequences play in the onset of the disease but may also allow new potential therapies to be developed.
© 1997 Roberto Deyes. Printed with Permission.
The Mad Scientist Network
Washington University School of Medicine
St. Louis, Missouri, USA
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