Early nonsense: mRNA decay solves a translational problem
Nadia Amrani, Matthew S. Sachs and Allan Jacobson
[Here are some excerpts:]
The nonsense-mediated mRNA decay (NMD) pathway ensures that incomplete messenger RNAs that harbour premature termination, or nonsense (non Amino acid coding), codons are targeted for rapid degradation. New insights into the process of NMD have provided unexpected glimpses of the complexity of translation termination.
Gene expression is highly accurate and rarely generates defective proteins. Several mechanisms ensure this fidelity, including specialized surveillance pathways that rid the cell of mRNAs that are incompletely processed or that lack complete open reading frames.
Given the overall congruity of gene expression mechanisms from yeast to humans, and the obvious need for quality control, it comes as no surprise that the nonsense mediated mRNA decay (NMD) pathway is active in all eukaryotes that have been examined, and that the three core factors of this pathway are highly conserved.
Existing models for the respective mechanisms of NMD in yeast and mammalian cells are not easily reconciled.
We propose a model for NMD in yeast in which the underlying mechanism that causes an mRNA to become an NMD substrate is compatible with mRNA processing, translation and degradative activities in all eukaryotes.
Current concepts of the mechanism of translation termination are vastly oversimplified.
The comparably complicated process of initiation is already known to involve as many as 100 factors.
Other studies of the modulation of eRF activity indicate considerable regulation of the termination process and the probable involvement of numerous additional factors.
The complexities of termination remain to be unravelled.