Science, 9 October, 2025, DOI：https://doi.org/10.1126/science.adu3433

Mechanism of DNA targeting by human LINE-1

Wenxing Jin, Cong Yu, Yan Zhang, Changchang Cao, Tianfan Xia, Ge Song, Zhaokui Cai, Yuanchao Xue, Bing Zhu, and Rui-Ming Xu

Abstract

Retrotransposons copy and insert their coding sequences into new genomic locations via RNA intermediates, posing risks to genome integrity. In humans, the only autonomously active retrotransposon is the long interspersed nuclear element–1 (LINE-1), which invades the genome through target-primed reverse transcription (TPRT). This process is catalyzed by the LINE-1–encoded open reading frame 2 protein (ORF2p), which has endonuclease (EN) and reverse transcriptase (RT) activities. In this study, we investigated the molecular mechanisms governing LINE-1 genome targeting and TPRT execution by ORF2p.

Article link：https://www.science.org/doi/10.1126/science.adu3433?sessionid=