DEGRADATION OF MESSENGER-RNA IN EUKARYOTES

Based on the above mechanisms of mRNA degradation, an integrated model of mRNA turnover can be proposed (Figure 1). In this model, all polyadenylated mRNAs would be degraded by the deadenylation-dependent pathway at some rate. In addition to this default pathway, another layer of complexity would come from degradation mechanisms specific to individual mRNAs or to classes of mRNAs. Such mRNA-specific mechanisms would include sequence-specific endonuclease cleavage and deadenylation-independent decapping. Thus, the overall decay rate of an individual transcript will be a function of its susceptibility to these turnover pathways. In addition, cis-acting sequences that specify mRNA decay rate, as well as regulatory inputs that control mRNA turnover, are likely to affect all the steps of these decay pathways. One important goal in future work will be to identify the gene products that are responsible for the nucleolytic events in these pathways and to delineate how specific mRNA features act to affect the function of these degradative activities. The identification of distinct mRNA decay pathways should allow genetic and biochemical approaches that can be designed to identify these gene products. A second important goal is to understand the nature of the interaction between the 5′ and 3′ termini, which may also be critical for efficient translation. © 1995.