Long Non-Coding RNAs in Primate Brain Evolution

灵长类动物大脑进化中的长非编码RNA

• 批准号: 254895102
• 负责人: Professorin Dr. Katja Nowick
• 金额: --
• 依托单位: Institut für Biologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/254895102?language=en
• 关键词: Long; Non; Coding; RNAs; Primate

Long non-coding RNAs (lncRNAs) have been identified as key players in the nervous system. Tens of thousands of lncRNAs are expressed in the brain, contribute to important brain functions and show associations with neurodegenerative and psychiatric diseases. Despite considerable efforts, there is still a large gap in the structural and in particular functional annotation of lncRNAs limiting our understanding of their role in the nervous system. Many characteristics of the brain are human specific. Genes that evolve quickly, as lncRNAs do, are therefore the best candidates to be primarily responsible for the evolution of these innovations. Since biological function has to be studied in the light of evolution, we aim here at establishing a full catalog of human lncRNAs, including an annotation of their sequence, structure, expression, and evolutionary changes by collating and coherently re-analyzing the wealth of already available high throughout data. In the first funding phase we have compiled a catalog of evolutionarily young, mostly brain-related lncRNAs, developed a generic, efficient algorithm for the reconstruction of transcript structures from diverse RNA-Seq data, and devised a statistical test for positive selection on lncRNAs. On this basis, we now want to focus on the functional evolution of lncRNAs. We propose to investigate evolutionary changes in lncRNAs across mammals including archaic humans, develop methods for distinguishing lncRNAs that function primarily based on their structure vs. on their primary sequence, predict and compare lncRNA target genes in primates, and relate evolutionary changes to complex brainfunctions and disorders. It is further our goal to provide our lncRNA catalog with its detailed annotations and functional information to the scientific community in a user-friendly manner.

长非编码 RNA (lncRNA) 已被确定为神经系统的关键参与者。数以万计的 lncRNA 在大脑中表达，有助于重要的大脑功能，并与神经退行性疾病和精神疾病相关。尽管付出了巨大的努力，lncRNA 的结构、特别是功能注释仍然存在很大差距，限制了我们对其在神经系统中作用的理解。大脑的许多特征是人类特有的。因此，像 lncRNA 一样快速进化的基因是主要负责这些创新进化的最佳候选基因。由于生物功能必须从进化的角度进行研究，我们的目标是建立人类lncRNA的完整目录，包括通过整理和连贯地重新分析大量现有的高通量数据来注释它们的序列、结构、表达和进化变化。在第一个资助阶段，我们编制了一个进化上年轻的、主要与大脑相关的 lncRNA 目录，开发了一种通用、有效的算法，用于从不同的 RNA-Seq 数据重建转录本结构，并设计了对 lncRNA 进行正选择的统计测试。在此基础上，我们现在要关注lncRNA的功能进化。我们建议研究包括古人类在内的哺乳动物中lncRNA的进化变化，开发主要根据其结构与一级序列来区分lncRNA的方法，预测和比较灵长类动物中的lncRNA靶基因，并将进化变化与复杂的脑功能和疾病联系起来。我们的进一步目标是以用户友好的方式向科学界提供我们的 lncRNA 目录及其详细注释和功能信息。