A key finding was that the outcome and function of À1 RF differs significantly between the viral and 'cellular' contexts. In viruses, PRF controls the stoichiometries of structural versus enzymatic proteins (18) . In contrast, 'cellular' RF events redirect elongating ribosomes to premature termination codons, suggesting that À1 RF is used to control cellular mRNA abundance and stability through the nonsense-mediated mRNA decay (NMD) pathway. While PRF is required for the production of functional products, in the cellular context RF appears to operate in a different manner. Thus, in the current work, PRF is used to connote frameshift signals whose function is to produce C-terminally extended proteins with novel functions, while RF is used to refer to frameshift signals that operate to direct ribosomes to premature termination codons. A proof-of-principle experiment demonstrated that a viral À1 PRF signal can function as an mRNA destabilizing element and that mRNA destabilization required NMD (19) . Here, rapid degradation of a reporter mRNA through NMD is demonstrated for four cellular yeast À1 RF signals. Further, genetic evidence suggests that the presence of the RF-stimulating pseudoknot may promote mRNA destabilization through the no-go decay (NGD) pathway (20) . The EST2 gene, encoding the catalytic subunit of telomerase (21) , was used to delve deeper into the relationships between À1 RF and mRNA stability. The EST2 mRNA is destabilized by À1 RF primarily via NMD. Ablation of its five À1 RF signals resulted in stabilization of the EST2 mRNA, and an inverse correlation between À1 RF efficiency and EST2 mRNA steady-steady state abundance was observed.