ABSTRACT
N onsense-mediated mRNA decay (NMD) is an evolutionary conserved cellular mechanism that reduces errors in eukaryotic gene expression by eliminating mRNAs that undergo aberrant translation termination. Two processes must be implemented for NM D to be achieved: recognition of an mRNA as aberrant’, and subsequent targeting of the substrate for accelerated degradation. Studies of NM D in Saccharomyces cerevisiae have led to a working model for RNA discrimination wherein premature and normal translation termina tion events are distinct due to the spatial relationship between the termination codon and downstream cis-acting sequences and proteins that bind to these sequences. Improper transla tion termination then leads to both translational repression and an increased susceptibility of the mRNA to multiple pathways of decay. Findings from yeast have provided an important framework for understanding the more complex events that occur during NM D in organisms such as Drosophila and mammals.
