Are long intergenic non-coding RNAs central regulators of inflammation and the innate immune response?

在人类基因组计划完成后，最大的惊喜是人类拥有的基因远远少于之前预期的(约2.1万)。此外，只有不到2%的可用DNA直接编码这些基因。为了解决这一悖论，最近的研究表明，剩下的98%的DNA中有很大一部分被转化为“非编码RNA”，这些RNA是基因表达的重要调节因素。为了方便起见，我们通常将这种非编码RNA分为小的非编码RNA和长的非编码RNA。目前，我们对大多数非编码RNA的作用知之甚少，尽管最近的研究表明，特定的非编码RNA可能调节免疫反应。为了抵抗细菌、真菌和病毒的感染，人体有一个复杂的防御系统，称为免疫反应。这涉及到对这些微生物的识别，并释放一系列化学物质来招募和激活免疫细胞(炎症)，这些细胞参与清除这些不受欢迎的入侵者。在正常情况下，这种炎症反应会被关闭。然而，在某些情况下，长时间的激活可能危及生命或导致哮喘、糖尿病、癌症和心血管疾病等常见疾病的发展。因此，重要的是要了解调节这种免疫反应的激活和抑制的机制。以前的研究表明，这种免疫反应是由一系列称为microRNAs的非编码小RNA改变的。然而，长的非编码RNA是否也可能是重要的还不得而知。在初步研究中，我们已经表明，在细胞中，在用细菌制成的产品刺激后，一些长非编码基因的水平会增加。我们还发现，其中一个长的非编码RNA调节着用于杀死入侵微生物的化学物质的释放。在这个项目中，我们将扩展这些研究，以检查其他长非编码RNA的功能以及它们可能如何发挥作用。总体而言，我们认为这些研究将表明，长的非编码RNA是炎症和对入侵病原体的免疫反应的重要调节因子。

Upon completion of the human genome project, the biggest surprise was that humans have far fewer genes than previously expected (~ 21,000). Additionally, less than 2% of the available DNA directly codes for these genes. To address this paradox, recent studies have suggested that much of the remaining 98% of DNA is turned into 'non-coding RNA' and that these are important regulators of gene expression. For convenience, we commonly divide this non-coding RNA into small non-coding RNAs and long non-coding RNAs. At the present time, we have little idea about the role of the majority of this non-coding RNA although recent studies have indicated that specific non-coding RNAs may regulate the immune response. In order to fight infection by bacteria, fungi and viruses, the body has a complex defense system called the immune response. This involves the recognition of these micro-organisms and release of a range of chemicals that recruit and activate immune cells (inflammation) that are involved in removing these un-wanted invaders. Under normal conditions, this inflammatory response is then switched off. However, under certain circumstances, prolonged activation can be life-threatening or lead to the development of common conditions such as asthma, diabetes, cancer and cardiovascular disease. For this reason it is important to understand the mechanisms that regulate both the activation and inhibition of this immune response. Previous studies have shown that this immune response is altered by a family of small non-coding RNAs, called microRNAs. However, whether long non-coding RNAs might also be important is unknown. In preliminary studies, we have shown that the levels of a number of long non-coding is increased in cells following stimulation with a product made from bacteria. We also found that one of these long non-coding RNAs regulates the release of the chemicals that are used to kill the invading micro-organisms. In this project, we will extend these studies to examine what other long non-coding RNAs do and how they might exert their actions. Overall, we believe that these investigations will show that long non-coding RNAs are important regulators of inflammation and the immune response to invading pathogens.