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

长基因间非编码 RNA 是炎症和先天免疫反应的中心调节因子吗？

• 批准号: BB/K006223/1
• 负责人: Mark Lindsay
• 金额: $ 40.91万
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK006223%2F1
• 关键词: long; intergenic; non; coding; RNAs

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.

在人类基因组计划完成后，最大的惊喜是人类的基因比以前预期的要少得多（约21，000个）。此外，只有不到2%的可用DNA直接编码这些基因。为了解决这一矛盾，最近的研究表明，剩余的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子。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，我们对大多数这种非编码RNA的作用知之甚少，尽管最近的研究表明特定的非编码RNA可以调节免疫应答。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。这涉及识别这些微生物并释放一系列化学物质，这些化学物质招募和激活免疫细胞（炎症），这些免疫细胞参与清除这些不需要的入侵者。在正常情况下，这种炎症反应被关闭。然而，在某些情况下，长期激活可能危及生命或导致常见疾病的发展，如哮喘，糖尿病，癌症和心血管疾病。出于这个原因，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个小的非编码RNA家族改变的，称为microRNA。然而，长的非编码RNA是否也很重要还不清楚。在初步研究中，我们已经表明，在用由细菌制成的产品刺激后，细胞中许多长非编码的水平增加。我们还发现，这些长的非编码RNA中的一个调节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，以研究其他长非编码RNA的作用以及它们如何发挥作用。总的来说，我们相信这些研究将表明长非编码RNA是炎症和对入侵病原体的免疫反应的重要调节因子。

项目成果

Transcriptional profiling identifies differential expression of long non-coding RNAs in Jo-1 associated and inclusion body myositis.

• DOI: 10.1038/s41598-017-08603-9
• 发表时间: 2017-08-14
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hamann PD;Roux BT;Heward JA;Love S;McHugh NJ;Jones SW;Lindsay MA
• 通讯作者: Lindsay MA

Divergent signalling pathways regulate lipopolysaccharide-induced eRNA expression in human monocytic THP1 cells.

• DOI: 10.1016/j.febslet.2014.12.026
• 发表时间: 2015-01-30
• 期刊: FEBS letters
• 影响因子: 3.5
• 作者: Heward JA;Roux BT;Lindsay MA
• 通讯作者: Lindsay MA

G protein-coupled receptors: what a difference a 'partner' makes.

• DOI: 10.3390/ijms15011112
• 发表时间: 2014-01-16
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Roux BT;Cottrell GS
• 通讯作者: Cottrell GS

Role of non-coding RNAs in maintaining primary airway smooth muscle cells.

• DOI: 10.1186/1465-9921-15-58
• 发表时间: 2014-05-16
• 期刊: Respiratory research
• 影响因子: 5.8
• 作者: Perry MM;Tsitsiou E;Austin PJ;Lindsay MA;Gibeon DS;Adcock IM;Chung KF
• 通讯作者: Chung KF

Long non-coding RNAs in the regulation of the immune response.

• DOI: 10.1016/j.it.2014.07.005
• 发表时间: 2014-09
• 期刊: Trends in immunology
• 影响因子: 16.8
• 作者: Heward JA;Lindsay MA
• 通讯作者: Lindsay MA