Abstract
R2 elements serve as a class of non-long terminal repeat (non-LTR) retrotransposons found in animal genomes that specifically insert into the ribosomal DNA (rDNA) sequences of host genomes. Each R2 element contains a single open reading frame (ORF) encoding a multifunctional protein with nucleic acid-binding, reverse transcriptase, and endonuclease activities, enabling specific genomic integration via a mechanism called target-primed reverse transcription (TPRT). As a classical model for studying retrotransposition mechanisms, R2 elements possess unique biological properties and precise integration capabilities, which have inspired novel genome engineering strategies. In this review, we summarize the components and integration mechanisms of R2 retrotransposons and highlight the recent advances in employing these mobile elements for targeted gene integration. Finally, we present future directions for the utilization of R2 retrotransposons as novel biotechnological tools.