Reverse transcriptase-related genes and their biological significance

逆转录酶相关基因及其生物学意义

• 批准号: 2326038
• 负责人: Irina Arkhipova
• 金额: $ 84.05万
• 依托单位: Marine Biological Laboratory
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2326038&HistoricalAwards=false
• 关键词: Reverse; transcriptase; related; genes; their

Reverse transcription converts RNA into DNA, in contrast to the typical flow of genetic information from DNA to RNA. Enzymes capable of DNA polymerization on RNA templates are called reverse transcriptases (RTs). RTs are believed to have played a major role in the transition from the primordial RNA world to the modern DNA-based forms of life. Since then, however, RT activity has mostly been employed by various selfish mobile genetic elements, such as retrotransposons or retroviruses. Beneficial uses of RT in cells are exceptionally rare, with eukaryotic telomerases being the only known example. The discovery by the researcher of single-copy reverse transcriptase-related genes with an intact active center, representing the only type of RTs present in both bacteria and eukaryotes, provides a unique opportunity to investigate the evolution of beneficial RT functions across different domains of Life. The function of these genes and their products will be studied by molecular, genetic, biochemical, and physiological methods, focusing on their response to environmental perturbations. Furthermore, the project involves extensive training for summer undergraduates by engaging them in individual research projects, providing the much-needed research experience as they prepare for graduate school applications and/or explore other career paths.To gain insights into the process of recruitment of an RNA-dependent polymerase into the metabolic environment of prokaryotic and eukaryotic cells, genetic screens aimed at dissecting regulatory pathways in model filamentous fungi will be combined with biochemical and functional assays in response to specific stress conditions, which will also be performed in native and heterologous systems such as rotifers and bacteria. The proposed research would uncover the nature of the evolutionary adaptation of RNA-dependent DNA synthesis for purposes entirely different from those previously examined, with the emergence of beneficial functions provided by additional domains endowing the host species with extra layers of flexibility in response to environmental stresses. Functional comparisons with the telomerase system should help to define the prerequisites for RT domestication. Finally, comparative analysis of different RT types would represent an essential step towards closure of the remaining gaps in the overall picture of RT structure, function, and evolution.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.

逆转录将RNA转化为DNA，与遗传信息从DNA到RNA的典型流动相反。能够在RNA模板上聚合DNA的酶被称为逆转录酶（RT）。据信RT在从原始RNA世界到基于DNA的现代生命形式的转变中发挥了重要作用。然而，从那时起，RT活性主要被各种自私的移动的遗传元件所利用，如反转录转座子或逆转录病毒。RT在细胞中的有益用途非常罕见，真核端粒酶是唯一已知的例子。研究人员发现了具有完整活性中心的单拷贝逆转录酶相关基因，代表了细菌和真核生物中存在的唯一类型的RT，为研究不同生命领域中有益RT功能的进化提供了独特的机会。这些基因及其产物的功能将通过分子、遗传、生物化学和生理学方法进行研究，重点是它们对环境扰动的反应。此外，该项目还包括对暑期本科生进行广泛的培训，让他们参与个人研究项目，为他们准备研究生院申请和/或探索其他职业道路提供急需的研究经验。为了深入了解RNA依赖性聚合酶在原核和真核细胞代谢环境中的招募过程，旨在剖析模型丝状真菌中的调节途径的遗传筛选将与响应特定胁迫条件的生物化学和功能测定相结合，这也将在天然和异源系统如轮虫和细菌中进行。拟议的研究将揭示RNA依赖的DNA合成的进化适应的性质，其目的与以前研究的完全不同，通过额外的结构域赋予宿主物种额外的灵活性来应对环境压力，从而出现有益的功能。与端粒酶系统的功能比较应有助于确定RT驯化的先决条件。最后，对不同RT类型的比较分析将代表着在RT结构、功能和演变的整体图景中关闭剩余差距的重要一步。该奖项反映了NSF的法定使命，并被认为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来支持。