ABSTRACT
Introduction The NM D pathway is operational in all eukaryotic organisms, ranging from single-cell fungi
to metazoans, including humans. As reviewed elsewhere in this volume (see chapters by Baker and Parker, Maquat, Behm-Ansmant and Izaurralde, Anderson, and van Hoof and Green), the core function of the NM D pathway is to degrade mRNAs containing premature termination codons (PTCs). PTCs can arise in mRNAs due to gene mutations, errors in transcription, or errors in RNA processing. NM D preserves the quality of the transcriptome and promotes organismal survival through the elimination of aberrant mRNAs, which have the potential to encode truncated proteins that could poison intracellular regulatory pathways (see chapters by Holbrook et al and Sharifi and Dietz). It is tempting to draw some conceptual parallels between the NM D machinery and the genome surveillance network, which detects and repairs damaged DNA before mutations become fixed in the genome. Indeed, the DNA repair apparatus comple ments the NM D system, in that both surveillance mechanisms play crucial roles in the mainte nance of transcriptome fidelity. However, NM D is much more than simply a cytoprotective mechanism against abnormal mRNAs. Eukaryotic cells rely heavily on alternative slicing of pre-mRNAs and NM D to regulate gene expression during development or in response to changing environmental conditions1’2 (see chapters by Shafari and Dietz and Soergel et al). Recent evi dence also indicates that the tandem processes of alternative mRNA splicing and NM D are centrally involved in the determination of cell fate-survival or death by apoptosis.3
