March 22, 2002 -- Research teams from two Howard Hughes Medical Institute (HHMI) laboratories have identified a new mechanism that cells use to recognize and destroy abnormal messenger RNA (mRNA). It is likely that cells employ the new mechanism, called nonstop decay, to target and destroy RNA molecules that contain errors.

Although nonstop decay is a normal RNA-policing mechanism, the researchers suggest that it might interfere with some drug treatments for cystic fibrosis and other genetic diseases. The new studies suggest that nonstop decay can be thwarted, which may make drug treatments for these diseases more effective.

The discovery of nonstop decay is reported in the March 22, 2002, issue of the journal Science by research teams led by HHMI investigators Harry C. Dietzat The Johns Hopkins University School of Medicine, and Roy R. Parker at the University of Arizona.

Messenger RNA molecules are the genetic templates for proteins. In constructing proteins, the mRNA template is transcribed from DNA genes and transported to the ribosomes the cells protein factories that are large complexes of protein and RNA. Given the importance of mRNA as an information-carrying molecule, the machinery that regulates mRNA levels and destroys faulty mRNA is critical in ensuring that errors in the genetic code are not passed on to proteins.

According to Dietz, his research team first believed that nonstop decay was similar to nonsense-mediated decay, the cells principal mechanism for destroying faulty mRNA that contains abnormal early stop signals called nonsense codons. Many genetic mutations or errors in transcribing mRNA result in nonsense codons that fail to code for any amino acids, the building blocks of proteins.

At the beginning, we had the hypothesis that an mRNA nonstop trans
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
21-Mar-2002