EAGER: Elucidating the basis of retrotransposon target preference

Transposition mechanisms of Penelope-like elements are one of the last uncharacterized mechanism of retromobility in eukaryotes. Establishment of a tractable system to dissect the mechanism and target preferences of these elements would not only advance our basic understanding of naturally occurring genome rearrangements but may also help design novel gene delivery systems in eukaryotes.

The project will provide support for a summer undergraduate internship to train a student in microbiology and molecular biology techniques in the context of intensive summer research atmosphere at the MBL.

Retrotransposons are mobile genetic elements, i.e., fragments of DNA that are inserted in the genomes of multicellular organisms, but may replicate autonomously, using virus-like mechanisms of making RNA and then reverse transcribing it. The two main retrotransposon subclasse are the LTR-and non-LTR (LINE) retrotransposons and the third major subclass, named Penelope-like elements has been found only recently and is not well-studied.

Interestingly, and unlike the other two classes of retrotransposons, Penelope-like elements appear to locate in those regions of the genome where the nucleotide sequence is arranged into the so-called (TA)n microsatellites, i.e., multiple repetitions of just two nucleotides. Such repetitions are rarely found within active protein-coding genes, and in this project, researchers are seeking to define the molecular details of how the retroelements 'find' where to integrate.

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.