Elucidating the role of long non-coding RNAs in the innate immune response: Identification of functional domains that regulate inflammation

人类基因组计划完成后，最令人惊讶的是，人类拥有的基因比之前预期的要少得多(约19,000个)，而且这是由不到2%的可用DNA编码的。值得注意的是，最近的研究表明，剩下的98%的DNA中有很大一部分变成了非编码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，我们对这种非编码RNA的大部分的作用知之甚少，尽管最近的研究表明，它们可能调节免疫反应。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。此前的研究表明，免疫反应由一系列称为microRNAs的非编码小RNA控制。值得注意的是，我们有初步证据表明，长的非编码RNA也可能是先天免疫的新调节器，特别是通过控制用于杀死入侵微生物的化学物质的释放。在这个项目中，我们将通过识别在人类和小鼠细胞中调节这种炎症反应的长非编码RNA来扩展这些研究。使用这些信息，我们将识别和验证在调节它们的行动中重要的序列。总体而言，这些研究将帮助我们了解长的非编码RNA作为炎症和对入侵病原体的免疫反应的调节器所起的作用。

Upon completion of the human genome project, the biggest surprise was that humans have far fewer genes than previously expected (~ 19,000) and that this is coded by less than 2% of the available DNA. Significantly, 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 these 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 microorganisms 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 the immune response is controlled by a family of small non-coding RNAs called microRNAs. Significantly, we have preliminary evidence showing that long non-coding RNAs might also be novel regulators of innate immunity, specifically by controlling the release of the chemicals used to kill the invading microorganisms. In this project, we will extend these studies by identifying those long non-coding RNAs that regulate this inflammatory response in both human and mouse cells. Using this information, we will then identify and validate the sequences that are important in mediating their actions. Overall, these investigations will help us understand the role of long non-coding RNAs as regulators of inflammation and the immune response to invading pathogens.