Characterization of Novel miRNAs During Development

开发过程中新型 miRNA 的表征

• 批准号: 7067103
• 负责人: Aurora Esquela Kerscher
• 金额: $ 5.04万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7067103
• 关键词: Caenorhabditis elegans; RNA; antisense nucleic acid; biochemical evolution; developmental genetics; embryo /fetus; gene induction /repression; genetic manipulation; genetically modified animals; helminth genetics; in situ hybridization; laboratory mouse; mature animal; northern blottings; postdoctoral investigator; species difference

DESCRIPTION (provided by applicant): MicroRNAs belong to a novel class of gene regulatory molecules found in plants and animals that control gene expression by binding to complimentary sequences on target mRNAs. Hundreds of miRNAs have recently been identified in worm, fly, and mammalian genomes. The function of only five miRNAs has been elucidated in animals and all five control important developmental processes. The uncharacterized miRNAs may also act as important gene regulators during development. Thirty C. elegans miRNAs are temporally regulated during development, eleven of which share homology to mammalian miRNAs. The hypothesis to be tested is that conserved temporally expressed miRNAs essential for C. elegans development will also be important during mammalian development. This proposal will 1) characterize the expression patterns of six novel conserved and temporally regulated miRNAs in C. elegans 2) determine the role of select conserved and temporally regulated miRNAs during C. elegans development and 3) investigate the function of one or two promising temporally regulated miRNA homologues in the mouse. These studies will contribute to the understanding of gene regulation and development and may lead to valuable insights on human disease.

描述（由申请人提供）： microRNA属于在动植物中发现的一类新的基因调节分子，这些分子通过与靶mRNA上的免费序列结合来控制基因表达。最近在蠕虫，苍蝇和哺乳动物基因组中发现了数百个miRNA。仅在动物和所有五个控制重要发育过程中阐明了五个miRNA的功能。未表征的miRNA在发育过程中也可以充当重要的基因调节剂。在发育过程中，有30枚秀丽隐杆线虫miRNA受到时间的调节，其中11个与哺乳动物miRNA具有同源性。要检验的假设是，在哺乳动物发育过程中，对秀丽隐杆线虫发育必不可少的暂时表达的miRNA也将很重要。该建议将1）表征秀丽隐杆线虫中六种新型保守和暂时调节的miRNA的表达模式2）确定秀丽隐杆线虫发育过程中精选保守和时间调节的miRNA的作用； 3）研究小鼠中一两个有前途的时间受到暂时调节的miRNA同源物的功能。这些研究将有助于理解基因调节和发育，并可能导致对人类疾病的宝贵见解。

项目成果

The mir-34 microRNA is required for the DNA damage response in vivo in C. elegans and in vitro in human breast cancer cells.

• DOI: 10.1038/onc.2009.106
• 发表时间: 2009-06-25
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Kato, M.;Paranjape, T.;Ullrich, R.;Nallur, S.;Gillespie, E.;Keane, K.;Esquela-Kerscher, A.;Weidhaas, J. B.;Slack, F. J.
• 通讯作者: Slack, F. J.