25 The Interface between mRNA Turnover and Translational Control

Abstract

The abundance of an mRNA is determined by the balance between transcription and decay. Thus, not surprisingly, a large percentage of the change in gene expression in response to stimuli can be attributed to regulated mRNA turnover (Garcia-Martinez et al. 2004). However, the relationship between mRNA stability and translation is complex: Some mRNAs can be very stable but produce virtually no protein (Mukhopadhyay et al. 2003), whereas other unstable mRNAs are efficiently translated (Kontoyiannis et al. 1999). This reflects, in part, the fact that an mRNA can assume three states: active translation, translationally silent, and targeted for decay. The issue is further complicated when we take into account that progress from one state to another is not necessarily linear and that there are multiple mRNA turnover pathways. Moreover, the mechanisms that regulate translation and turnover are so intricately interwoven that we are only just beginning to unravel the details. For example, some experiments suggest that translation is absolutely necessary for ongoing mRNA decay; inhibition of translation elongation with cycloheximide stabilizes the vast majority of cellular transcripts (Herrick et al. 1990). In contrast, other data argue that translation and turnover are in direct competition; a reduction in translation initiation efficiency can lead to destabilization of mRNAs (Schwartz and Parker 1999).

To help the reader understand the complex nature of the translation/turnover paradox, our goal is to describe the various pathways and enzymes of mRNA decay, highlighting interactions with the translation process. We go on to discuss the recent finding that mRNAs...