One critical clue that the nonsense and nonstop mechanisms were different emerged from the work of Pamela A. Frischmeyer, in Dietzs laboratory, who showed in experiments in yeast that nonstop decay shared none of the enzymes required for nonsense-mediated decay. We found that nonstop decay was an entirely new mRNA turnover mechanism that had none of the properties of nonsense-mediated decay, or of normal mRNA turnover in the cell, said Dietz. Additional experiments showed that the same nonstop decay mechanism found in yeast was also conserved in mammalian cells, he said.
Once we recognized this conservation, the question arose as to why evolution would develop and maintain this mechanism, said Dietz. When the scientists searched genomic databases, they found a surprise: One percent of genes in both humans and yeast produce mRNAs containing specific sequences that would trigger degradation of the RNA by nonstop decay.
These sequences were often conserved through evolution in a given message, said Dietz. If the net result was simply to be wasteful, to cause degeneration of transcripts, then we would expect that they would not be conserved. But the fact that they were conserved suggests that these nonstop transcripts, and the proteins that could result from them, may have some importance in normal development.
According to Dietz, nonstop mRNA transcripts might be important in enabling production of shortened proteins that are needed at specific stages of development. At later stages of development, when these truncated proteins are no longer needed, their mRNA could easily be destroyed by nonstop decay.
Dietz and his colleagues also explored whether nonstop decay reduces the effectiveness of drugs currently being tested to treat geneti
Contact: Jim Keeley
Howard Hughes Medical Institute