URoL: Epigenetics 2: Profiling and functional dissection of the epitranscriptome in archaeal extremophiles

URoL：表观遗传学 2：古菌极端微生物表观转录组的分析和功能解剖

• 批准号: 2022065
• 负责人: Thomas Santangelo
• 金额: $ 300万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2022065&HistoricalAwards=false
• 关键词: URoL; Epigenetics; Profiling; functional; dissection

Chemical modifications to RNA molecules, which produce the so-called epitranscriptome, are prevalent in all forms of life. The functions of RNA modifications are yet unclear, although some modifications are thought to control the stability of the RNA. The goal of this project is to establish the patterns and functions of chemical modifications to protein-coding messenger RNAs (mRNAs) in the Archaea. This is especially important for Archaea, which thrive under extreme conditions - temperature, salinity, pressure, or pH - that are destabilizing for RNAs of most life forms. By studying mRNA modifications from Archaea in comparison to other organisms, this research is expected to establish Rules of mRNA Modification that will contribute to better understanding of the functional importance of this evolutionarily conserved process. The research results will be documented in a new web-based platform, called the mRNA Modification Database. This database will serve the broader RNA research community, STEM researchers, and the public. This research will be conducted by an interdisciplinary team involving researchers from academic, government, and industry labs, which will offer students the opportunity to engage in collaborative research across different professional settings. This project seeks to expand understanding of the rules for establishment and function of the epitranscriptome in Archaea. A combination of unbiased techniques and genome-scale mapping methods will be used to identify, map, and compare the totality of ribonucleoside modifications present in a diverse range of extremophilic Archaea. Changes to the epitranscriptome due to environmental insults and specific genetic alterations will be determined. In parallel, experiments will be conducted to identify and characterize a suite of archaeal enzymes responsible for generating the archaeal epitranscriptome. A key aim is to establish the targeting sequences that result in site- and modification-specific alterations of select mRNAs. The rules of mRNA selection and targeting by each enzyme will be iteratively tested in vitro and then in vivo. Datasets, together with mapping techniques, mass spectrometry standards, and chemical and enzymatic characterizations of RNA modification enzymes, will be catalogued in a web-based mRNA Modification Database, which will be serve as a research and public resource. This project is funded by the Understanding the Rules of Life: Epigenetics Program, administered as part of NSF's Ten Big Ideas through the Division of Emerging Frontiers in the Directorate for Biological Sciences. Co-funding is provided by the Genetic Mechanisms Program, Division of Molecular and Cellular Biosciences, Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

对RNA分子的化学修饰，即产生所谓的表转录组，在所有形式的生命中都很普遍。 RNA修饰的功能尚不清楚，尽管一些修饰被认为控制RNA的稳定性。 本项目的目标是建立化学修饰的模式和功能的蛋白质编码信使RNA（mRNA）的的在Escherichia。 这对于在极端条件下茁壮成长的海蛞蝓来说尤其重要-温度，盐度，压力或pH值-这些条件对大多数生命形式的RNA都是不稳定的。 通过研究与其他生物体相比，从古生物的mRNA修饰，这项研究预计将建立mRNA修饰的规则，这将有助于更好地理解这一进化保守过程的功能重要性。 研究结果将记录在一个新的基于网络的平台上，称为mRNA修饰数据库。 该数据库将服务于更广泛的RNA研究社区，STEM研究人员和公众。 这项研究将由一个跨学科的团队进行，其中包括来自学术，政府和行业实验室的研究人员，这将为学生提供在不同专业环境中进行合作研究的机会。 该项目旨在扩大对Escherichia中epitranscriptome的建立和功能规则的理解。 无偏技术和基因组规模的映射方法的组合将被用来识别，映射，并比较核糖核苷修饰存在于各种极端嗜热菌的总体。将确定由于环境损伤和特定遗传改变引起的表位转录组的变化。 同时，将进行实验以鉴定和表征一套负责产生古细菌表转录组的古细菌酶。一个关键的目标是建立靶向序列，导致选择mRNA的位点特异性和修饰特异性改变。每种酶的mRNA选择和靶向规则将在体外然后在体内反复测试。数据集，连同映射技术，质谱标准，以及RNA修饰酶的化学和酶的表征，将被编目在一个基于网络的mRNA修饰数据库，这将作为一个研究和公共资源。该项目由理解生命规则：表观遗传学计划资助，该计划作为NSF十大理念的一部分，通过生物科学理事会新兴前沿部门进行管理。共同资助是由遗传机制计划，分子和细胞生物科学司，生物科学理事会。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。