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，而不是典型的遗传信息流从DNA到RNA。能够在RNA模板上进行DNA聚合的酶称为逆转录酶(RT)。RTS被认为在从原始RNA世界向以DNA为基础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，真核细胞端粒酶是唯一已知的例子。这位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，为研究生命不同领域中有益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、生化和生理方法进行研究，重点是它们对环境扰动的反应。此外，该项目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，在他们准备研究生院申请和/或探索其他职业道路时提供急需的研究经验。为了深入了解依赖RNA的聚合酶在原核和真核细胞的代谢环境中的招募过程，旨在剖析模型丝状真菌调控途径的遗传筛选将与生物化学和功能分析相结合，以响应特定的应激条件，这也将在轮虫和细菌等本地和异源系统中进行。拟议的研究将揭示依赖RNA的DNA合成的进化适应的性质，目的与先前研究的完全不同，因为额外的结构域提供了有益的功能，赋予寄主物种额外的灵活性层来应对环境压力。与端粒酶系统的功能比较应该有助于确定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朝着弥合RT结构、功能和进化的整体图景中的剩余差距迈出的重要一步。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。