Long interspersed nuclear element-1 reverse transcriptase (LINE-1 RT or L1 ORF2p)

Long interspersed nuclear element-1 reverse transcriptase is the enzymatic component encoded by the ORF2 gene of LINE-1 (L1) retrotransposons, which are abundant, autonomous mobile genetic elements in the human genome[1][2][5][8]. The protein, commonly called L1 ORF2p, possesses both reverse transcriptase and endonuclease activity and is essential for retrotransposition, enabling LINE-1 to copy and paste itself into new genomic locations through a process called target-primed reverse transcription (TPRT)[3][4][6]. In addition to mobilizing its own sequences, L1 ORF2p can mobilize non-autonomous retroelements such as Alu and generate processed pseudogenes[5][8]. Abnormally high LINE-1 reverse transcriptase activity is implicated in cancer, autoimmunity, and ageing, and experimental inhibition of LINE-1 RT can restore normal gene expression and suppress tumor progression[2][7][8]. ORF2p and its reverse transcriptase activity can also impact small RNA biogenesis, activate innate immunity (via RNA:DNA hybrid formation and cGAS/STING activation), and contribute to genome instability. Only a small subset of the ~500,000 LINE-1 copies in the human genome encodes a functional ORF2 protein, but these are sufficient to maintain active retrotransposition[2][4][5]. Due to its dual enzymatic activity, central role in genome dynamics, and relevance to disease, LINE-1 reverse transcriptase is increasingly seen as a potential therapeutic target, with various classes of reverse transcriptase inhibitors investigated in preclinical models[2][7][8].

Other names

LINE-1 reverse transcriptaseL1 reverse transcriptaseL1 RTORF2pLINE-1 ORF2 protein

Inhibition of reverse transcriptase enzymatic activity Blocking LINE-1 retrotransposition Modulation of gene expression via retroelement suppression