Sometimes it’s the RNA

Common scientific wisdom is that inherited disease results when a mutated protein communicates a defective message in the cell. That does not explain how similar mutations in proteins result in different severities of diseases.

The answer may be found in the messenger RNA (ribonucleic acid), said Dr. James Lupski, professor of molecular and human genetics and pediatrics at Baylor College of Medicine and colleagues in a report that appears online in Nature Genetics on March 8, 2004.

The stability of the messenger RNA is critical. Aberrant forms of messenger RNA are usually eliminated by a mechanism called nonsense-mediated decay. In some mutations, messenger RNA will be affected by the decay mechanism but in others, it escapes it and causes fabrication of a defective protein. In general, when the mutated RNA falls victim to the decay mechanism, the disease is usually milder than when it escapes it all together.

Lupski and his colleagues have demonstrated the role of RNA in mutations in a gene called SOX10 and another called MPZ. Each is associated with diseases of varying severity that affect the nervous system.

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