An Evolutionary Link Between Telomeres and Transposons

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

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.