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.

基因包含制造使细胞和使其起作用的蛋白质所需的信息。这些信息从存储点（DNA）传递到用来通过称为Messenger RNA（mRNA）的分子制成特定蛋白质的点。尽管这些信息传输是一个相对准确的过程，但还是犯了错误。 DNA重排，突变积累，并且在互连信息时会产生错误。其中一些错误可能会欺骗细胞制造错误的蛋白质，这将是正确蛋白质的截断变体。不幸的是，这种异常蛋白通常具有与正常蛋白质竞争的能力，并以细胞过程的正确功能造成破坏。因此，截短的蛋白质对生物体可能非常危险，这对细胞防止其制造是一个优势。所有真核生物都有识别和破坏可能编码截短蛋白质产品的异常mRNA的机制。这些机制被称为废话介导的mRNA衰变（NMD），该提案旨在了解植物中的NMD。对于细胞而言，识别可能编码不正确蛋白质以及细胞如何管理此壮举的mRNA并不是一个琐碎的任务。从本质上讲，植物如何将“好” mRNA与“坏” mRNA区分开。重要的是在植物中研究NMD很重要。首先，尽管NMD在哺乳动物，蠕虫，苍蝇和酵母中进行了很好的研究，但在这些模型生物体中已经发现了NMD机理的主要差异。例如，在哺乳动物中，看来剪接（将mRNA的碎片连接在一起）对于NMD识别异常mRNA至关重要，因为将蛋白质复合物（称为EJC）添加到mRNA中以标记剪接点，并为NMD机制提供固定的参考点，以筛选出错误。因此，NMD机制似乎对未剪接的哺乳动物mRNA不起作用。但是，大多数酵母（酿酒酵母）mRNA并未剪接，因此依赖于剪接的NMD系统几乎是没有用的。因此，酵母使用另一种方法来识别异常mRNA。苍蝇具有许多剪接基因和EJC蛋白，但NMD与苍蝇中的EJC无关。我们几乎不知道植物中的NMD。与哺乳动物不同，有证据表明植物中的mRNA触发了NMD，这表明尽管其他系统可以为检查NMD提供一个框架，但我们需要独立定义规则。我们没有一组共识规则，可以应用于工厂NMD。其次，越来越明显的是，NMD机制并不仅仅存在淘汰不良mRNA。哺乳动物和酵母的研究表明，NMD机制实际上代表了基因表达的全球系统，并且细胞中超过10％的基因在该机制的控制之下。我们再次不知道这对植物是否正确，或者是否会发现植物和其他生物中NMD控制的一组基因。最后，有一些证据表明，在蠕虫中，NMD机制与调节基因表达RNAi的另一种重要方法有关。 RNAi可用于在包括植物在内的几种模型生物中下调基因表达。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节方法之间的链接，其中两个过程相交。看到诱变对缺乏NMD的植物后观察到什么影响也将非常有趣。在这样的植物中，人们可能期望看到许多表型作用，这是由于截短的蛋白质的表达而产生的，这些作用会在正常植物中抑制。