The Interplay between Eukaryotic mRNA Degradation and Translation

The destruction of mRNA is a critical aspect of gene regulation. All mRNA must be destroyed to ensure that nuclear regulatory decisions are manifested as cytoplasmic events. In other words, ceasing mRNA transcription in response to environmental or physiological cues is irrelevant as long as cytoplasmic mRNA exists and is translated. All mRNA must, therefore, die. From this, it can be said that mRNA decay contributes significantly to the proteomes' overall architecture by allowing cells to quickly adapt to environmental and physiological change. Although much is known about mRNA decay in eukaryotes, understanding how the process is modulated is far from complete. mRNA translation is known to be tightly integrated with mRNA decay. In the last few years, work has concentrated on this relationship as a means to elucidate regulation. From this, two views have arisen. The first suggests that mRNA must be removed from ribosomes to be destroyed in ribosome-free areas, such as P-bodies. The other view proposes mRNA decay occurs in concert with protein synthesis. In this article we summarize our current understanding on how eukaryotic mRNA decay interconnects with mRNA translation, and then analyze the data that have lead to these two diametrically opposed models on where mRNA decay occurs within the cell. Finally we attempt to reconcile these two views and suggest important areas for future investigation.