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

阐明长非编码 RNA 在先天免疫反应中的作用：鉴定调节炎症的功能域

• 批准号: BB/N015630/1
• 负责人: Mark Lindsay
• 金额: $ 52.22万
• 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: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN015630%2F1
• 关键词: Elucidating; role; long; non; coding

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.

人类基因组计划完成后，最大的惊喜是人类拥有的基因比之前预期的要少得多（约 19,000 个），而且由不到 2% 的可用 DNA 编码。值得注意的是，最近的研究表明，剩余 98% 的 DNA 中的大部分转化为“非编码 RNA”，并且这些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分为小非编码RNA和长非编码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这些非编码 RNA 可能调节免疫反应。为了对抗细菌、真菌和病毒的感染，身体有一个复杂的防御系统，称为免疫反应。这涉及到识别这些微生物并释放一系列化学物质，这些化学物质招募并激活免疫细胞（炎症），从而参与清除这些不需要的入侵者。在正常情况下，这种炎症反应随后就会关闭。然而，在某些情况下，长时间激活可能会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生。因此，了解调节这种免疫反应的激活和抑制的机制非常重要。先前的研究表明，免疫反应是由一类称为 microRNA 的小非编码 RNA 控制的。值得注意的是，我们有初步证据表明，长非编码RNA也可能是先天免疫的新型调节剂，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，我们将通过鉴定那些调节人类和小鼠细胞炎症反应的长非编码RNA来扩展这些研究。使用这些信息，我们将识别并验证对于调解他们的行为很重要的序列。总的来说，这些研究将帮助我们了解长链非编码 RNA 作为炎症调节剂和对入侵病原体的免疫反应的作用。

项目成果

Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response.

• DOI: 10.3389/fimmu.2017.01038
• 发表时间: 2017
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Roux BT;Heward JA;Donnelly LE;Jones SW;Lindsay MA
• 通讯作者: Lindsay MA

Direct Determination of the Mutation Rate in the Bumblebee Reveals Evidence for Weak Recombination-Associated Mutation and an Approximate Rate Constancy in Insects.

直接测定大黄蜂的突变率揭示了昆虫中弱重组相关突变和近似速率恒定性的证据

• DOI: 10.1093/molbev/msw226
• 发表时间: 2017-01
• 期刊: Molecular biology and evolution
• 影响因子: 10.7
• 作者: Liu H;Jia Y;Sun X;Tian D;Hurst LD;Yang S
• 通讯作者: Yang S

Supplementary Methods;Paper II.Supplementary Methods-20160810.docx from Mutation rate analysis via parent-progeny sequencing of the perennial peach II: no evidence for recombination-associated mutation

补充方法；论文 II.补充方法-20160810.docx，来自多年生桃子通过亲子测序进行突变率分析 II：没有重组相关突变的证据

• DOI: 10.6084/m9.figshare.4009944
• 发表时间: 2016
• 作者: Wang L

Paper II.Supp.Figures.and.Tables-20160812.docx; from Mutation rate analysis via parent-progeny sequencing of the perennial peach II: no evidence for recombination-associated mutation

论文 II.Supp.Figures.and.Tables-20160812.docx；

• DOI: 10.6084/m9.figshare.4009950
• 发表时间: 2016
• 作者: Wang L