Curbing the nonsense: the activation and regulation of mRNA surveillance: Figure 1.

Gene expression requires the coordination and integration of multiple processes, including transcription, splicing, polyadenylation, nucleocytoplasmic export, and translation of mRNAs. Such complexity inevitably results in errors, many of which ultimately lead to premature termination of translation. Additionally, nonsense mutations can be introduced during DNA replication and are the cause of 20% to 40% of human genetic diseases (Frischmeyer and Dietz 1999). The truncated proteins encoded by these mutant mRNAs are potentially toxic to the cell, and therefore, a mechanism, known as mRNA surveillance or nonsense-mediated mRNA decay (NMD), has evolved to recognize mRNAs containing premature termination codons (PTCs) and cause their degradation to be accelerated.