Nonsense mediated mRNA decay in plants

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Genes contain the information necessary to make the proteins that make cells and make them work. This information is carried from the points of storage (DNA) to the points at which it is used to make specific proteins by a molecule called messenger RNA (mRNA). Despite this information transfer being a relatively accurate process, mistakes are made. DNA rearranges, mutations accumulate and errors are made in interconverting the information. Some of these errors could fool the cell into making incorrect proteins, which will be truncated variants of the correct protein. Unfortunately, such aberrant proteins often have the ability to compete with the normal proteins and create havoc with the correct functioning of cellular processes. Truncated proteins are therefore potentially very dangerous for the organism and it would be an advantage to the cell to prevent them from being made. All eukaryotes have mechanisms to identify and destroy aberrant mRNAs which might encode truncated protein products. The mechanisms are known as nonsense-mediated mRNA decay (NMD) and this proposal seeks to understand NMD in plants. It is not a trivial task for a cell to recognise an mRNA which might encode an incorrect protein and how cells manage this feat is of great topical interest. In essence would like to understand how a plant distinguishes 'good' mRNA from 'bad' mRNA. It is important to study NMD in plants for three main reasons. Firstly, although NMD has been well studied in mammals, worms, flies and yeast, major differences in the mechanism of NMD have been discovered in these model organisms. For example, in mammals it appears that splicing (joining together bits of mRNA) is essential for NMD to recognise aberrant mRNA, because a protein complex (called the EJC) is added to the mRNA to mark the splice points and to provide fixed reference points for the NMD mechanism to screen for errors. As a result of this, the NMD mechanism appears not to work on mammalian mRNAs that are not spliced. However, most yeast (S. cereviseae) mRNAs are not spliced, so a splicing-dependent NMD system would be almost useless. Consequently, yeast uses a different method to identify aberrant mRNAs. Flies have both lots of spliced genes and EJC proteins, but NMD is independent of the EJC in flies. We have almost no idea about NMD in plants. Unlike in mammals, there is evidence that unspliced mRNAs trigger NMD in plants, showing that although other systems can provide a framework for examining NMD, we need to define the rules independently. There is no set of consensus rules that we can apply to plant NMD. Secondly, it is becoming increasingly obvious that the NMD mechanism does not solely exist to weed out bad mRNA. Research in mammals and yeast has shown that the NMD mechanism actually represents a global system of gene expression and that more than 10% of the genes in the cell are under the control of this mechanism. Once again we have no idea whether this will be true for plants or whether overlapping sets of genes will be found to be controlled by NMD in plants and other organisms. Finally, there is some evidence that in worms the NMD mechanism is linked to another important method to regulate gene expression, RNAi. RNAi can be used to downregulate gene expression in several model organisms, including plants. We have evidence that plants which are defective in the NMD process are also deficient in RNAi. We need to explore the link between these two methods of regulatione where the two processes intersect. It will also be very interesting to see what effect is observed following mutagenesis on plants lacking NMD. In such plants one might expect to see a host of phenotypic effects, resulting from the expression of truncated proteins, that would be suppressed in normal plants.