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: 7002193
• 负责人: ELISABETTA ULLU
• 金额: $ 31.93万
• 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/7002193
• 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，这些途径在一只手上充当了针对核酸入侵者（例如病毒，移动元件和异常转录本）的防御机制，另一方面与基因表达的调节有关。 RNA干扰或RNAi是指这样的途径，是转录后基因沉默机制，通过该机制，基因特异性双链RNA（DSRNA）触发同源细胞转录物的降解。小型非编码RNA（小型干扰RNA或siRNA）的发现是该过程的标志，很快就会意识到，在核和细胞质隔室中，小型非编码RNA参与了几种不同水平的真核基因表达。对Brucei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位置及其生物学。锥虫原生动物是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沉默的机制可能使我们了解了这种机制及其生物学意义的演变。此外，鉴于在锥虫中，大多数基因调节发生在转录后水平上，因此RNA沉默可能在基因表达的调节中起着核心作用。的确，我们提供了证据表明，RNAi在锥虫中的生物学功能之一是使逆向转录本沉默，以防止或减少重新构成及其对基因组完整性的有害作用。该提案的长期目标是了解Brucei T. brucei中小RNA的生物学功能，其特定目的是：1。克隆和表征Brucei中的小型非编码RNA，并研究其他动型乳腺癌中是否存在类似的RNA。 2。分析RNAi在T. Brucei中消融的生物学后果。 3。研究RNAi机制消融对基因表达的后果。