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)： MicroRNAs是一类在植物和动物中发现的新型基因调控分子，它通过与靶mRNAs上的互补序列结合来控制基因的表达。最近在蠕虫、苍蝇和哺乳动物的基因组中发现了数百个miRNAs。只有5个miRNAs在动物中的功能已被阐明，所有5个miRNAs都控制着重要的发育过程。这些未知的miRNAs也可能在发育过程中发挥重要的基因调节作用。30个线虫miRNAs在发育过程中受时间调控，其中11个与哺乳动物miRNAs同源。需要检验的假设是，保守的时间表达的miRNAs对线虫的发育至关重要，在哺乳动物的发育过程中也是重要的。这一建议将1)表征6个新的保守和时间调节的miRNAs在线虫中的表达模式；2)确定选择的保守的和时间调节的miRNAs在线虫发育过程中的作用；3)研究一个或两个有希望的时间调节的miRNA同源物在小鼠中的功能。这些研究将有助于理解基因调控和发育，并可能导致对人类疾病的有价值的见解。

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.