Function and evolution of microRNAs

microRNA的功能和进化

• 批准号: 7123958
• 负责人: Fabio Piano
• 金额: $ 18.68万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-21 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123958
• 关键词: Nematoda; antisense nucleic acid; binding sites; biochemical evolution; bioinformatics; biotechnology; computational biology; computer program /software; developmental genetics; functional /structural genomics; gene expression; gene induction /repression; helminth genetics; high throughput technology; messenger RNA; microRNAs; molecular biology information system; molecular genetics; nucleic acid inhibitor; oligonucleotides; site directed mutagenesis; species difference

DESCRIPTION (provided by applicant): Recent experiments have shown that the genomes of organisms such as worm, fly, human, and mouse encode hundreds of novel microRNA genes. Many of these small non-coding genes are thought to regulate the translational expression of other genes by binding to partially complementary sites in target messenger RNAs. Initial phenotypic and expression analyses suggest an important role for microRNAs in basic cellular processes such as development, viral response, and apoptosis. Furthermore, many microRNAs are conserved over large evolutionary distances. However, the biological function of most microRNAs is unknown. Although recent computational methods have made progress towards the identification of microRNA targets, no experimental high-throughput method for dissecting microRNA function exists. Our long-term goal is to create a system where bioinformatic and experimental methods are integrated to make possible the high-throughput combinatorial analysis of microRNA function. Here, we propose to setup this system. Specifically, we will (a) employ in silica methods to predict microRNA targets in five different nematode species, (b) use inhibitor oligonucleotides to knock down the function of 20 microRNAs across several nematode species in vivo, and register their loss-of-function phenotypes throughout development, (c) develop a system to validate predicted microRNA targets in vivo and test 25 computationally predicted targets. These data will generate novel insights into the biological function of microRNAs and their potential role in shaping biological diversity. This project is an intensive collaboration between a bioinformatics lab (focused on gene regulatory processes), and an experimental lab (RNAi functional genomics in nematodes)

描述（由申请人提供）：最近的实验表明，诸如蠕虫，苍蝇，人和小鼠等生物的基因组编码了数百种新型microRNA基因。这些小型非编码基因中的许多都被认为可以通过与目标信使RNA中的部分互补位点结合来调节其他基因的翻译表达。初始表型和表达分析表明，在基本细胞过程中，例如发育，病毒反应和凋亡中，microRNA的重要作用。此外，许多microRNA在较大的进化距离上是保守的。但是，大多数microRNA的生物学功能尚不清楚。尽管最近的计算方法已取得了鉴定microRNA靶标的进展，但不存在用于剖析microRNA功能的实验高通量方法。我们的长期目标是创建一个集成生物信息学和实验方法的系统，以使MicroRNA功能的高通量组合分析成为可能。在这里，我们建议设置此系统。 Specifically, we will (a) employ in silica methods to predict microRNA targets in five different nematode species, (b) use inhibitor oligonucleotides to knock down the function of 20 microRNAs across several nematode species in vivo, and register their loss-of-function phenotypes throughout development, (c) develop a system to validate predicted microRNA targets in vivo and test 25 computationally predicted targets.这些数据将产生对microRNA的生物学功能及其在塑造生物学多样性中的潜在作用的新见解。该项目是生物信息学实验室（侧重于基因调节过程）与实验实验室（线虫中的RNAi功能基因组学）之间的密集合作。