A biological rationale for NMD in plants

植物中 NMD 的生物学原理

• 批准号: BB/H00775X/1
• 负责人: Brendan Davies
• 金额: $ 45.86万
• 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: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH00775X%2F1
• 关键词: biological; rationale; NMD; plants

Animals, fungi and plants split a long time ago and have evolved very different life strategies. Nevertheless, clues to their common origin can be found in the form of conserved processes carried out using many of the same components in all eukaryotes. Gene expression is one such process and the ability to turn genes on and off, up and down is fundamental to life. There are many ways to regulate gene activity. One of the least studied involves regulating the stability of molecules known as mRNA; the messenger signals that move from the genes in the nucleus to where the proteins are made in the cytoplasm. Recently, it has been discovered that a mechanism called NMD, that used to be considered as a sort of quality control sift for mRNA, destroying 'bad' mRNA before it ordered the production of the wrong proteins, actually oversees lots of different mRNAs, including many that appear to be normal. A working estimate of the total number of genes that could typically be inspected by NMD could be as many as 5% - perhaps 1500 genes. Why would a cell go to the expense of copying lots of genes into mRNA only to quickly destroy the mRNA again before its instructions could be acted upon? We have been looking at mutant plants where NMD is not working properly, both by studying the consequences for the plant as a whole and by looking at the effect on all of the plant's mRNA levels. These analyses have identified a potential biological rationale for what appears to be an energetically wasteful arrangement. Our work indicates that plants use NMD to suppress the levels of mRNAs that they will need quickly if they find themselves exposed to an environmental challenge, such as a change in the climate of a pathogen attack. This makes sense because by stopping NMD from destroying specific mRNA the plant can make those mRNAs stable, so that they can be translated many times over to make the necessary proteins to deal with the challenge the plant faces. Presently we have a list of both indirect and direct NMD targets in the plant cell. To dissect the interaction between the environment and co-ordinated gene regulation via mRNA stability we first need to identify both the direct targets and which of the conserved components are required to specify which target. At that point we can make artificial targets so that we can study how the environment signals to NMD and we can tease out the full range of responses mediated by this ancient process. This research could have applied benefits in terms of understanding plant interactions with pathogens and the environment and also by providing the tools to artificially conditionally regulate the stability and hence translatability of mRNA messages.

动物、真菌和植物很久以前就分裂了，并进化出了截然不同的生活策略。然而，它们共同起源的线索可以通过在所有真核生物中使用许多相同组件进行的保守过程的形式找到。基因表达就是这样一个过程，打开和关闭基因、升高和降低基因的能力是生命的基础。调节基因活性的方法有很多。研究最少的一项涉及调节 mRNA 分子的稳定性；从细胞核中的基因转移到细胞质中产生蛋白质的地方的信使信号。最近，人们发现一种叫做 NMD 的机制，过去被认为是一种 mRNA 的质量控制筛选，在命令生产错误的蛋白质之前摧毁“坏”的 mRNA，实际上监督着许多不同的 mRNA，包括许多看起来正常的 mRNA。对 NMD 通常可检查的基因总数的工作估计可能多达 5%——也许是 1500 个基因。为什么细胞会不惜代价将大量基因复制到 mRNA 中，却在其指令得到执行之前再次快速破坏 mRNA？我们一直在研究 NMD 不能正常发挥作用的突变植物，既研究对整个植物的影响，又观察对植物所有 mRNA 水平的影响。这些分析已经确定了这种看似能源浪费的安排的潜在生物学原理。我们的工作表明，如果植物发现自己面临环境挑战，例如病原体攻击的气候变化，植物会使用 NMD 来抑制它们快速需要的 mRNA 水平。这是有道理的，因为通过阻止 NMD 破坏特定的 mRNA，植物可以使这些 mRNA 稳定，这样它们就可以多次翻译，生成必要的蛋白质来应对植物面临的挑战。目前，我们有植物细胞中间接和直接 NMD 靶标的列表。为了通过 mRNA 稳定性剖析环境与协调基因调控之间的相互作用，我们首先需要确定直接靶标以及需要哪些保守成分来指定哪个靶标。那时我们可以制作人工目标，以便我们可以研究环境如何向 NMD 发出信号，并且我们可以梳理出由这一古老过程介导的全方位反应。这项研究可以在理解植物与病原体和环境的相互作用方面发挥作用，也可以通过提供人为条件调节 mRNA 信息的稳定性和可翻译性的工具来发挥作用。

项目成果

Conservation of Nonsense-Mediated mRNA Decay Complex Components Throughout Eukaryotic Evolution.

• DOI: 10.1038/s41598-017-16942-w
• 发表时间: 2017-11-30
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Causier B;Li Z;De Smet R;Lloyd JPB;Van de Peer Y;Davies B
• 通讯作者: Davies B

The salicylic acid dependent and independent effects of NMD in plants.

• DOI: 10.4161/psb.21960
• 发表时间: 2012-11
• 期刊: Plant signaling & behavior
• 影响因子: 2.9
• 作者: Rayson S;Ashworth M;de Torres Zabala M;Grant M;Davies B
• 通讯作者: Davies B

A role for nonsense-mediated mRNA decay in plants: pathogen responses are induced in Arabidopsis thaliana NMD mutants.

• DOI: 10.1371/journal.pone.0031917
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Rayson S;Arciga-Reyes L;Wootton L;De Torres Zabala M;Truman W;Graham N;Grant M;Davies B
• 通讯作者: Davies B

The loss of SMG1 causes defects in quality control pathways in Physcomitrella patens.

• DOI: 10.1093/nar/gky225
• 发表时间: 2018-06-20
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Lloyd JPB;Lang D;Zimmer AD;Causier B;Reski R;Davies B
• 通讯作者: Davies B