Regulation of gene expression by novel plant-specific small nucleolar RNAs

植物的多样性，植物如何生长发育，以及它们对外界刺激的反应，如病原体/害虫的攻击或胁迫条件，都取决于植物物种的基因含量和基因表达的调控。基因在许多不同的水平上受到调控。一个重要的层面是基因在哪里被开启或关闭或上调或下调--称为转录控制。第二个水平发生在基因转录或复制到RNA之后--称为转录后调控。在这一层面上，RNA可以以不同的方式处理，或者作为破坏或降解的目标。转录后调控有许多不同的机制，其中最重要的是选择性剪接和小RNA分子的靶向。选择性剪接是指基因转录本的不同部分以不同的组合连接在一起，从一个基因产生一个以上的信使RNA(MRNA)。由此产生的mRNAs可以被翻译成具有不同功能的蛋白质，或者可以作为降解的目标。小RNA分子如microRNAs(MiRNAs)或Short-intering RNAs(SiRNAs)可以与靶mRNAs碱基配对并诱导其降解，从而沉默靶基因的表达。这引入了通过其他通常是小的调控RNA的碱基配对的特定相互作用来调控mRNAs的概念。细胞中的许多基本过程依赖于与其他较大的RNA物种相互作用的小RNA的活性。例如，在核糖体中发现的核糖体RNA(RRNA)的产生需要小核仁RNA(SnoRNAs)来将前体rRNA切割成特定的rRNA。信使RNA是由前体RNA通过剪接过程产生的，在剪接过程中内含子被识别和移除。这个过程依赖于小的核RNA来识别内含子信号和剪接反应本身。最近，数以百计的miRNAs和siRNAs被确定为通过促进靶mRNAs的降解或干扰其翻译来调节表达。虽然不同的小RNA家族被认为与相当特定的靶RNA集合相互作用并进行调控，但已经发现了一些例子，其中小RNA获得了其他小RNA的特征，因此它们的功能范围并不像之前认为的那样受到限制。SnoRNAs通过碱基配对参与rRNA的生产。在动物中，已经发现了一些不与rRNA碱基配对但可以与mRNAs碱基配对的snoRNAs(称为孤儿snoRNAs)。一些人类孤儿snoRNAs能够影响mRNAs的选择性剪接，显示了snoRNAs新功能的进化。我们在植物中发现了孤立的snoRNAs，特别是一组全新的、植物特有的snoRNAs。这些snoRNAs与mRNAs具有互补性，本方案的主要目的是将这些新的snoRNAs及其与mRNAs相互作用的意想不到的潜力描述为植物基因调控的一种新模式。了解基因调控各个方面的复杂性和微妙之处，对于了解植物如何生长和存活以及预测对变化的环境的反应是重要的。这种监管模式本身在表达控制领域是有意义的。此外，由于它依赖于一个稳定的RNA，可以与mRNAs靶向和碱基对，因此有可能修改snoRNA，以调节的方式靶向其他特定的基因和过程。这些信息将是旨在了解调控基因表达和生物过程的相互作用网络的系统方法的组成部分。

Plant diversity, how plants grow and develop, and how they respond to external stimuli such as attack by pathogens/pests or stress conditions, all depend on the gene content of the plant species and the regulation of expression of the genes. Genes are regulated at many different levels. One important level is where genes are turned on or off or up or down - called transcriptional control. A second level occurs after the gene is transcribed or copied into RNA - called post-transcriptional control. At this level RNAs can be processed in different ways or targeted for destruction or degradation. There are many different mechanisms of post-transcriptional control of which alternative splicing and targeting by small RNA molecules are two of the most important. Alternative splicing is where different portions of a gene transcript are joined in different combinations to generate more than one messenger RNA (mRNA) from a gene. The resultant mRNAs can be translated into proteins with different functions or can be targeted for degradation. Small RNA molecules such as microRNAs (miRNAs) or short-interfering RNAs (siRNAs) can base-pair with target mRNAs and induce their degradation thereby silencing expression of the target gene. This introduces the concept of regulation of mRNAs by the specific interaction via base-pairing of other, usually small, regulatory RNAs. Many essential processes in the cell depend on the activity of small RNAs interacting with other, larger RNA species. For example, the production of ribosomal RNA (rRNA) species found in ribosomes requires small nucleolar RNAs (snoRNAs) to cut the precursor rRNA into specific rRNAs. Messenger RNAs are produced from precursor mRNAs by the process of splicing where introns are recognised and removed. This process depends on small nuclear RNAs for recognition of intron signals and the splicing reaction itself. More recently, hundreds of miRNAs and siRNAs have been identified as regulators of expression by promoting degradation of target mRNAs or interfering with their translation. While different families of small RNAs are thought to interact with and regulate fairly specific sets of target RNAs, examples have been found where small RNAs have picked up the characteristics of other small RNAs such that their range of functionality is not as restricted as previously thought. SnoRNAs are involved in production of rRNA via base-pairing. In animals, some snoRNAs (called 'orphan' snoRNAs) have been found which do not base-pair with rRNAs but instead can base-pair with mRNAs. Some of the human orphan snoRNAs are able to affect alternative splicing of mRNAs showing the evolution of novel functions for snoRNAs. We have found orphan snoRNAs in plants and, in particular, a group of entirely novel, plant-specific snoRNAs. These snoRNAs have complementarity to mRNAs and the major thrust of this proposal is to characterise these new snoRNAs and their unexpected potential to functionally interaction with mRNAs as a new mode of gene regulation in plants. Knowledge of the complexity and subtlety of all aspects of gene regulation is important in understanding how plants grow and survive and in the prediction of responses to changing environments. This mode of regulation is of interest per se in the field of expression control. In addition, because it relies on a stable RNA which can target and base-pair with mRNAs, the potential exists to modify the snoRNA to target other specific genes and processes in a regulated manner. Such information will be an integral part of systems approaches aimed at understanding the interaction networks which regulate gene expression and biological processes.