WEHI Special ACRF Chemical Biology Seminar hosted by Professor Isabelle Lucet
 

Dr Max Wilkinson

Feng Zhang Lab, jointly at the Broad Institute and MIT

A structural basis for LINE retrotransposition

Davis Auditorium

Join via TEAMS

Including Q&A session

Non-LTR retrotransposons, or LINEs, are the most abundant mobile genetic elements in the human genome, and have the potential to be engineered for the insertion of large DNA sequences in mammalian genomes without forming double-strand DNA breaks. They spread by nicking target DNA and reverse transcribing their own RNA in situ, but the molecular principles governing their target site selection and self RNA specificity are not known. In this talk I will present the cryoEM structure of a Bombyx mori R2 non-LTR retrotransposon, caught in the act of inserting into the 28S ribosomal RNA gene. The structure shows how the retrotransposon locates its target DNA sequence using two key sequence motifs. Structural and biochemical analysis show how target DNA nicking is coupled to reverse transcription of the retrotransposon RNA, and how the retrotransposon specifically recognizes its own RNA. Based on these findings, I show that Cas9 can retarget LINEs in vitro to non-native sequences, suggesting future use as a reprogrammable RNA-based gene-insertion tool.

Max completed his BSc Honours with Peter Fineran at the University of Otago, NZ, before undertaking his PhD studies with Kiyoshi Nagai at the MRC-LMB in Cambridge, UK. He since moved to MIT and the Broad Institute where he is a postdoctoral fellow in the lab of Feng Zhang.

All welcome!