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Nonsense mediated mRNA decay in plants

植物中无义介导的 mRNA 衰变

基本信息

批准号：
BB/E001823/1
负责人：
Brendan Davies
金额：
$ 33.04万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2006
资助国家：
英国
起止时间：
2006 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FE001823%2F1
关键词：
Nonsense mediated mRNA decay plants

项目摘要

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.

基因包含制造制造细胞并使其工作的蛋白质所需的信息。这种信息被称为信使RNA(信使RNA)的分子从储存点(DNA)携带到用来制造特定蛋白质的点。尽管这种信息传递是一个相对准确的过程，但也会犯错误。DNA重排，突变累积，在信息相互转换过程中出错。其中一些错误可能会欺骗细胞制造错误的蛋白质，这些蛋白质将是正确蛋白质的截断变体。不幸的是，这种异常蛋白质往往具有与正常蛋白质竞争的能力，并对细胞过程的正常功能造成严重破坏。因此，截短的蛋白质对生物体来说是潜在的非常危险的，防止它们被制造出来对细胞来说是一种优势。所有真核生物都有识别和破坏可能编码截短蛋白产物的异常mRNAs的机制。这种机制被称为无意义介导的信使核糖核酸衰变(NMD)，这一提议试图了解植物中的NMD。对于细胞来说，识别可能编码错误蛋白质的信使核糖核酸并不是一项微不足道的任务，细胞如何实现这一壮举是人们非常感兴趣的话题。从本质上讲，我们想要了解植物如何区分“好”和“坏”的信使核糖核酸。研究植物中的NMD很重要，主要有三个原因。首先，虽然NMD在哺乳动物、蠕虫、苍蝇和酵母中已经得到了很好的研究，但在这些模式生物中发现了NMD机制的主要差异。例如，在哺乳动物中，似乎剪接(将几个片段的mRNA连接在一起)对于NMD识别异常的mRNA是必不可少的，因为一个蛋白质复合体(称为EJC)被添加到mRNA中来标记剪接点，并为NMD机制提供固定的参考点来筛选错误。因此，NMD机制似乎不适用于没有剪接的哺乳动物mRNA。然而，大多数酵母(S.cereviseae)的mRNAs不是剪接的，因此依赖剪接的NMD系统几乎是无用的。因此，酵母使用一种不同的方法来识别异常的mRNAs。果蝇同时具有大量的剪接基因和EJC蛋白，但NMD不依赖于果蝇的EJC。我们对植物中的NMD几乎一无所知。与哺乳动物不同，有证据表明未剪接的mRNA在植物中触发NMD，这表明尽管其他系统可以提供检查NMD的框架，但我们需要独立定义规则。没有一套共识规则可以适用于建立NMD。其次，越来越明显的是，NMD机制的存在不仅仅是为了淘汰不良的mRNA。在哺乳动物和酵母中的研究表明，NMD机制实际上代表了一个全球性的基因表达系统，细胞中超过10%的基因受到这一机制的控制。再说一次，我们不知道这是否适用于植物，或者是否会在植物和其他生物中发现重叠的基因集受NMD控制。最后，有一些证据表明，在蠕虫中，NMD机制与另一种调节基因表达的重要方法RNAi有关。RNAi可以用来下调包括植物在内的几种模式生物的基因表达。我们有证据表明，在NMD过程中有缺陷的植物也缺乏RNAi。我们需要探索这两种调控方法之间的联系，在这两个过程相交的地方。在缺乏NMD的植物上进行诱变后观察到什么影响也将是非常有趣的。在这类植物中，人们可能会看到一系列的表型效应，这些效应是由截短蛋白的表达导致的，而这些效应在正常植物中是被抑制的。