Aptamers in model organisms

模型生物中的适体

• 批准号: 1330606
• 负责人: Andrej Luptak
• 金额: $ 51万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1330606&HistoricalAwards=false
• 关键词: Aptamers; model; organisms

Intellectual meritRNAs are remarkable because they can be both information carriers and structured functional macromolecules. They play a wide variety of roles in biology, including in gene expression regulation by riboswitches. Riboswitches are metabolite-dependent functional RNAs composed of aptamer domains and expression platforms, which bind small-molecule targets and regulate gene expression, respectively. Most riboswitches have been found in bacteria, with a single example known in plants, fungi, and algae, where it regulates alternative splicing and transcript stability. To discover more eukaryotic riboswitches, small-molecule aptamers need to be mapped out and tested for regulatory functions. Recently, adenosine aptamers were discovered in the human genome and preliminary results indicate that they sense ATP through a kinetic mechanism. The objective of this project is to measure the distribution of a variety of metabolite aptamers in genetic model eukaryotes. The aptamers will be detected using in vitro selections from a metagenomic genomic library and tested for potential roles as riboswitches. Adenosine aptamers, together with new aptamers found using SELEX will be tested for gene regulatory functions. Altogether, this research will contribute to the fundamental understanding of eukaryotic RNA biology and help define the roles that non-coding functional RNAs play in gene regulation and other cellular mechanisms. Broader impactsThis project will enhance our understanding of regulatory roles that RNAs play in eukaryotic model organisms, including plants. Throughout the project period undergraduate and graduate students will be trained in molecular and cellular biosciences, providing them with sets of broadly applicable problem-solving skills on both in both experimental and computational biology. In addition, a large numbers of young students from local middle schools, many of them from backgrounds that do not emphasize education and from schools that lack the resources for laboratory experimentation, will be exposed to the thrill of molecular biology to encourage them to consider higher education in the sciences

智力熟人是出色的，因为它们既可以是信息携带者，又可以是结构化功能性大分子。他们在生物学中扮演着各种各样的角色，包括核糖开关的基因表达调节。核糖开关是由适体域和表达平台组成的代谢产物依赖性功能RNA，分别结合了小分子靶标并调节基因表达。大多数核糖开关都在细菌中发现，其中一个在植物，真菌和藻类中已知的例子，它调节了替代剪接和转录本稳定性。为了发现更多的真核核糖开关，需要将小分子适体绘制并测试调节功能。最近，在人类基因组中发现了腺苷适体，初步结果表明它们通过动力学机制感知ATP。该项目的目的是衡量遗传模型真核生物中各种代谢物适体的分布。将使用来自元基因组基因组文库的体外选择来检测适体，并测试了作为核糖开关的潜在作用。腺苷适体以及使用SELEX的新适体的基因调节功能将测试。总之，这项研究将有助于对真核RNA生物学的基本理解，并有助于定义非编码功能RNA在基因调节和其他细胞机制中起的作用。这一项目将增强我们对RNA在包括植物在内的真核模型生物中起作用的调节作用的理解。在整个项目期间，本科生和研究生将接受分子和细胞生物科学的培训，为他们提供一组在实验和计算生物学中的广泛适用问题的技能。此外，许多来自当地中学的年轻学生，其中许多来自不强调教育的背景以及缺乏实验室实验资源的学校，将暴露于分子生物学的刺激下，以鼓励他们在科学中考虑高等教育