Curbing the nonsense: the activation and regulation of mRNA surveillance

Gene expression requires the coordination and integration of multiple proce sses, including transcription, splicing, polyadenylation, nucleocytoplasmic export, and translation of mRNAs. Such complexity inevitably results in er rors, 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 pote ntially toxic to the cell, and therefore, a mechanism, known as mRNA survei llance or nonsense-mediated mRNA decay (NMD), has evolved to recognize mRNA s containing premature termination codons (PTCs) and cause their degradatio n to be accelerated.