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，与从DNA到RNA的典型遗传信息流相反。能够在RNA模板上进行DNA聚合的酶称为逆转录酶（RTS）。据信，RT在从原始RNA世界到基于现代DNA的生活形式的过渡中发挥了重要作用。但是，从那时起，RT活动主要由各种自私的移动遗传元素（例如逆转录病毒或逆转录病毒）采用。 RT在细胞中的有益用途异常罕见，真核端粒酶是唯一已知的例子。研究人员的单拷贝逆转录酶相关基因的发现，具有完整的活性中心，代表细菌和真核生物中存在的唯一类型的RT类型，为研究跨不同领域的有益RT功能的演变提供了独特的机会。这些基因及其产物的功能将通过分子，遗传，生化和生理方法研究，重点是它们对环境扰动的反应。此外，该项目涉及对夏季大学生的广泛培训，通过使他们参与各个研究项目，在为研究生院申请准备和/或探索其他职业途径时提供了急需的研究经验真菌将与特定应力条件响应生化和功能测定法结合，这也将在天然和异源系统（例如旋转液和细菌）中进行。拟议的研究将揭示RNA依赖性DNA合成的进化适应性的性质，目的与先前研究的目的完全不同，并出现了由其他域赋予宿主物种具有额外灵活性的其他域提供的有益功能，以响应环境应力。与端粒酶系统的功能比较应有助于定义RT驯化的先决条件。最后，对不同RT类型的比较分析将代表终止RT结构，功能和进化的整体差距的重要一步。该奖项反映了NSF的法定任务，并认为值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来获得支持。