Small RNAs and their role in trypanosome biology

小 RNA 及其在锥虫生物学中的作用

• 批准号: 6758532
• 负责人: ELISABETTA ULLU
• 金额: $ 32.7万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6758532
• 关键词: Small; RNAs; their; role; trypanosome

DESCRIPTION (provided by the applicant): All eukaryotic organisms possess gene silencing pathways that on one hand function as defense mechanisms against nucleic acid invaders such as viruses, mobile elements and aberrant transcripts, and on the other hand are involved in the regulation of gene expression. RNA interference or RNAi refers to one such pathway and is a post-transcriptional gene silencing mechanism through which gene-specific double-stranded RNA (dsRNA) triggers degradation of homologous cellular transcripts. The discovery that small non-coding RNAs (small interfering RNAs or siRNAs) are the hallmarks of this process was very soon followed by the realization that small non-coding RNAs are involved in regulating eukaryotic gene expression at several different levels, in both the nuclear and cytoplasmic compartments. The interest in Trypanosoma brucei as a model system to study RNAi and related RNA silencing mechanisms stems primarily from its evolutionary position and its biology. Trypanosomatid protozoa represent one of the deepest branches of the eukaryotic lineage and are therefore considered descendants of "ancient" eukaryotes. Thus, understanding the mechanism of RNA silencing in trypanosomes might give us clues to the evolution of this mechanism and to its biological significance. Furthermore, given that in trypanosomes most gene regulation takes place at the post-transcriptional level, there is the possibility that RNA silencing plays a central role in the regulation of gene expression. Indeed, we have provided evidence that one of the biological functions of RNAi in trypanosomes is to silence retroposon transcripts to most likely prevent or reduce retroposition and its deleterious effects on genome integrity. The long-term goal of this proposal is to understand the biological function of small RNAs in T. brucei with the following specific aims: 1. Clone and characterize small non-coding RNAs in T. brucei and investigate whether similar RNAs exist in other kinetoplastidae. 2. Analyze the biological consequences of ablation of RNAi in T. brucei. 3. Investigate the consequences of ablation of the RNAi mechanism on gene expression in T. brucei.

描述（由申请人提供）：所有真核生物都具有基因沉默途径，一方面作为针对病毒、移动元件和异常转录本等核酸入侵者的防御机制，另一方面参与基因表达的调节。 RNA干扰或RNAi就是这样的一种途径，是一种转录后基因沉默机制，基因特异性双链RNA (dsRNA)通过该机制触发同源细胞转录本的降解。发现小非编码 RNA（小干扰 RNA 或 siRNA）是这一过程的标志，很快人们就认识到小非编码 RNA 在几个不同的水平上参与调节真核基因表达，无论是在细胞核还是细胞核中。和细胞质区室。人们对布氏锥虫作为研究 RNAi 和相关 RNA 沉默机制的模型系统的兴趣主要源于其进化地位和生物学。锥虫原生动物代表真核谱系最深的分支之一，因此被认为是“古代”真核生物的后代。因此，了解锥虫中 RNA 沉默的机制可能为我们提供了解该机制的进化及其生物学意义的线索。此外，鉴于锥虫中大多数基因调控发生在转录后水平，RNA沉默有可能在基因表达调控中发挥核心作用。事实上，我们提供的证据表明，锥虫中 RNAi 的生物学功能之一是沉默逆转录子转录物，以最有可能防止或减少逆转录及其对基因组完整性的有害影响。该提案的长期目标是了解T. brucei中小RNA的生物学功能，具体目标如下： 1. 克隆和表征T. brucei中的小非编码RNA，并研究其他动质体中是否存在类似的RNA 。 2. 分析 T. brucei 中 RNAi 消融的生物学后果。 3. 研究 RNAi 机制消除对 T. brucei 基因表达的影响。