Role of the microRNA miR144 in haemopoiesis in vivo

微小RNA miR144在体内造血中的作用

• 批准号: nhmrc : 461222
• 负责人: Prof Graham Lieschke
• 金额: $ 26.16万
• 依托单位: The Walter and Eliza Hall Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-microrna-mir144-haemopoiesis-vivo/77615
• 关键词: Role; microRNA; miR144; haemopoiesis; vivo

Recently a new form of gene regulation has been discovered involving small RNA molecules called microRNAs (miRNAs). Although vertebrates (like man, mouse and fish) contain many hundreds of miRNAs, the function and true gene targets of each individual miRNA are largely unknown. A better understanding the normal function and targets of miRNAs is needed so that their role in normal biology and disease development can be understood. These studies exploit the technical strengths of zebrafish, an model of increasing importance in biomedical research, to study the function of a particular miRNA, miR144, and to identify its physiological target genes. Zebrafish have several advantages for studying miRNA function - several simple methods for experimentally altering miRNA levels are standard in zebrafish but not easy in other models like mice. miR144 has been chosen because it has an expression pattern that strongly suggests a role in blood development. Blood development and zebrafish technologies are central themes of the Lieschke laboratory. Preliminary experiments in zebrafish have shown that miR144 expression can be detected in blood cells, that it is functionally active when overexpressed, that its effect can be intercepted, and that there are blood-system effects of its misexpression, particularly in mutant zebrafish with abnormalities of blood development that provide a sensitized background for such studies. These studies will describe the expression of miR144 in detail in normal and abnormal zebrafish blood development. The effects of miR144 overexpression and knock-down of expression will be studied in detail. To identify the targets of mir144, a multifaceted microarray analysis will be performed, and the validity of candidate targets suggested by this will then be systematically tested. When finished, these studies will have characterised the physiology of this new blood regulator and identified the way it exerts its effect.

最近，一种新的基因调控形式被发现涉及到被称为microRNAs(MiRNAs)的小RNA分子。尽管脊椎动物(如人、老鼠和鱼)含有数百个miRNA，但每个miRNA的功能和真正的基因靶标在很大程度上是未知的。需要更好地了解miRNAs的正常功能和靶标，以便了解它们在正常生物学和疾病发展中的作用。这些研究利用斑马鱼的技术优势，研究特定miRNA miR144的功能，并确定其生理目标基因。斑马鱼是生物医学研究中日益重要的模型。斑马鱼在研究miRNA功能方面有几个优势--几种通过实验改变miRNA水平的简单方法在斑马鱼中是标准的，但在其他模型如小鼠中并不容易。之所以选择miR144，是因为它的表达模式强烈表明它在血液发育中发挥了作用。血液开发和斑马鱼技术是Lieschke实验室的中心主题。对斑马鱼的初步实验表明，可以在血细胞中检测到miR144的表达，当它过度表达时，它的功能是活跃的，它的作用可以被截获，它的错误表达会对血液系统产生影响，特别是在血液发育异常的突变斑马鱼中，这为此类研究提供了致敏的背景。这些研究将详细描述miR144在正常和异常斑马鱼血液发育中的表达。我们将详细研究miR144的过度表达和表达下调的影响。为了识别Mir144的目标，将进行多方面的微阵列分析，然后将系统地测试由此提出的候选目标的有效性。当这些研究完成后，这些研究将描述这种新的血液调节剂的生理特征，并确定它发挥作用的方式。