Reverse Transcriptase-Related Genes and Their Biological Significance

知识专长：逆转录酶是在RNA模板上进行DNA合成的酶。人们普遍认为，逆转录酶活性主要是由自私的遗传元件，如逆转录转座子和逆转录病毒，用于其自身的复制和繁殖。唯一已知的例外是端粒酶，它由单拷贝基因编码，并通过将相关RNA模板的一小部分重复复制到DNA上来维持真核生物的染色体末端。该项目旨在通过研究在不同真核生物中发现的新型逆转录酶相关基因，利用计算，生物化学和遗传方法来了解RNA依赖聚合的进化起源和细胞功能。系统发育分布和与其他类逆转录酶的关系，编码产物的酶活性，并可能参与细胞途径将被调查。这些研究可以揭示以前未知的作用RNA依赖聚合在活细胞中。阐明逆转录酶相关基因的进化起源和细胞功能具有根本的重要性，并有望对分子生物学、遗传学和进化等领域产生重大影响。这项研究的结果预计将挑战目前对RNA依赖性聚合作用的既定观点，这可能被严重低估。教育活动将包括研究生和本科生的培训，以及他们直接参与研究，这将导致学生合著的出版物。其他活动将包括：积极参加国家和国际科学会议，以确保向科学界成员更广泛地传播成果;组织区域会议，为信息交流和培训提供场所，并通过提供旅费赠款吸引少数民族与会者;积极参加当地高中的科学展览会。外联工作的目标是通过媒体采访和为面向更广泛受众的流行书籍撰稿，将国家科学基金会资助的研究成果带给非专业人员和公众。

Intellectual Merit: Reverse transcriptases are enzymes that perform DNA synthesis on RNA templates. It is widely believed that reverse transcriptase activity is mostly used by selfish genetic elements, such as retrotransposons and retroviruses, for their own replication and propagation. The only known exceptions are telomerases, which are encoded by single-copy genes and maintain eukaryotic chromosome ends by repeatedly copying a small region of the associated RNA template onto DNA. This project seeks to understand the evolutionary origins and cellular functions of RNA-dependent polymerization by studying novel reverse transcriptase-related genes found in diverse eukaryotes, using computational, biochemical, and genetic approaches. Phylogenetic distribution and relationships with other classes of reverse transcriptases, enzymatic activity of the encoded products, and possible involvement in cellular pathways will be investigated. These studies could reveal previously unknown roles for RNA-dependent polymerization in living cells. Elucidation of evolutionary origins and cellular functions of reverse transcriptase-related genes is of fundamental importance and may be expected to have a major impact on the fields of molecular biology, genetics, and evolution.Broader Impacts: The project will have both scientific and educational impacts. The results of the study are expected to challenge the currently established views on the role of RNA-dependent polymerization, which may be significantly under-appreciated. Educational activities will include training of graduate and undergraduate students and their direct involvement in research, which will result in student-coauthored publications. Other activities will include: active participation in national and international scientific meetings to ensure broader dissemination of the results to members of the scientific community; organization of regional meetings to provide venues for information exchange and training and, through travel grants, to attract minority participants; and active involvement in science fairs at local high schools. Outreach efforts will be aimed at bringing results of NSF-funded research to non-specialists and the general public through media interviews and contributions to popular books targeted at wider audiences.