Structural and biochemical studies of mobile retrotransposon proteins in action

Autonomous non-long-terminal repeat (non-LTR) retrotransposons, including long interspersed elements (LINEs), are mobile genetic elements abundant in eukaryotic species that shape the genomic landscape and host physiology in both health and disease. Non-LTR retrotransposons create new genomic copies through a mechanism termed target-primed reverse transcription, where the retrotransposon-encoded protein nicks target DNA to prime reverse transcription templated by bound RNA, typically its own encoding mRNA. Until recently, structural information on non-LTR retrotransposons was lacking due to challenges in purification and reconstitution of active complexes. Recent biochemical studies and cryo-electron microscopy structures of complexes from insect, bird, and turtle site-specific R2 retrotransposons and the human LINE-1 retrotransposon have provided important insights. Here we discuss these studies and their implications for retrotransposon evolution and eukaryotic genome biology.