An Evolutionary Link Between Telomeres and Transposons

我们建议扩展我们的分析显着的重复非长末端重复序列（non-LTR） 逆转录转座子，HeT-A，TART和Tahre，它们构成了果蝇的端粒。总体目标是：（1） 为了加深对转座子端粒进化的了解， 关于真核生物染色体和转座因子的进化问题，2）分析 逆转录转座子端粒的细胞生物学，因为这些变异的端粒可以帮助我们了解 端粒酶维持的端粒的生物学及其在人类健康中的作用，以及3）阐明它们在人类健康中的作用。 与宿主细胞共同进化我们将扩展我们的端粒生物学特性， 反转录转座子序列。pseudoobscura和D. virilis，使用这些物种之间的比较， D. melanogaster，以更好地了解端粒不可简化的必要特征。我们的工作 表明HeT-A和TART RNA可能具有意想不到的作用。我们将通过RNA测试这种可能性 在转基因果蝇和培养的细胞中的HeT-A和TART转录物的干扰（RNAi）敲低。我们有 发现HeT-A和TART的表达可以由几种外部因子调节。我们描述 实验，以更好地定义能够进行这种调节的试剂集，并探索可能的机制。

We propose to extend our analyses of the remarkable repeated non-Long Terminal Repeat (non-LTR) retrotransposons, HeT-A,TART, and Tahre, that make up Drosophila telomeres. The overarching aims are 1) to deepen insight into the evolution of transposon telomeres as a step to understanding more general questions concerning the evolution of both eukaryotic chromosomes and transposable elements, 2) to analyze the cell biology of retrotransposon telomeres because these variant telomeres can help us understand the biology of telomeres maintained by telomerase and their roles in human health, and 3) to elucidate their coevolution with their host cells. We will extend our characterization of the telomeric biology and retrotransposon sequences of D. pseudoobscura and D. virilis, using comparisons between these species and D. melanogaster to gain better insight into the irreducibly necessary features of telomeres. Our work has suggested that HeT-A and TART RNAs may have unexpected roles. We will test this possibility by RNA interference (RNAi) knockdown of HeT-A and TART transcripts in transgenic flies and cultured cells. We have discovered that HeT-A and TART expression can be regulated by several external agents. We describe experiments to better define the set of agents capable of this regulation and to explore possible mechanisms.