Long interspersed nuclear element-1 (LINE-1)

Long interspersed nuclear element-1 (LINE-1) is an autonomous non-LTR retrotransposon that comprises approximately 17% of the human genome [1, 15]. It functions through a 'copy-and-paste' mechanism where its RNA transcript is reverse-transcribed and integrated into new genomic locations, a process known as retrotransposition [9, 10]. LINE-1 encodes two essential proteins: ORF1p, an RNA-binding protein with nucleic acid chaperone activity, and ORF2p, which possesses both endonuclease and reverse transcriptase activities [9, 12]. While typically silenced in healthy adult tissues via DNA methylation, LINE-1 can be reactivated by environmental stress or during disease states, leading to genomic instability, DNA damage, and the activation of innate immune responses through the cGAS-STING pathway [1, 6, 18]. This reactivation is a hallmark of many cancers and is increasingly implicated in the pathogenesis of autoimmune disorders (e.g., Aicardi-Goutières syndrome) and neurodegenerative diseases like ALS and Alzheimer's [2, 4, 7]. Therapeutic strategies currently focus on inhibiting the reverse transcriptase activity of ORF2p using nucleoside reverse transcriptase inhibitors (NRTIs) or novel specific inhibitors to mitigate inflammation and genomic damage [6, 13, 19].

Other names

L1LINE1L1RE1Long interspersed element-1Non-LTR retrotransposon

Inhibition of the LINE-1 reverse transcriptase (ORF2p) to prevent the synthesis of cDNA from LINE-1 RNA, thereby blocking retrotransposition and the activation of the cGAS-STING innate immune signaling pathway [6, 18, 19].