Long interspersed nuclear element

[11] Based on structural features and the phylogeny of the essential protein ORF2p, LINEs can be separated into six main groups, referred to as R2, RanI, L1, RTE, I and Jockey.

[19] All LINEs encode a least one protein, ORF2, which contains an RT and an endonuclease (EN) domain, either an N-terminal APE or a C-terminal RLE or rarely both.

Except for the evolutionary ancient R2 and RTE superfamilies, LINEs usually encode for another protein named ORF1, which may contain an Gag-knuckle, a L1-like RRM (InterPro: IPR035300), and/or an esterase.

LINE elements are relatively rare compared to LTR-retrotransposons in plants, fungi or insects, but are dominant in vertebrates and especially in mammals, where they represent around 20% of the genome.[12]: fig.

[27] Increased L1 copy numbers have also been found in the brains of people with schizophrenia, indicating that LINE elements may play a role in some neuronal diseases.

ORF2 (and ORF1 when present) proteins primarily associate in cis with their encoding mRNA, forming a ribonucleoprotein (RNP) complex, likely composed of two ORF2s and an unknown number of ORF1 trimers.

[29] The complex is transported back into the nucleus, where the ORF2 endonuclease domain opens the DNA (at TTAAAA hexanucleotide motifs in mammals[30]).

For example, the RNA interference (RNAi) mechanism of small interfering RNAs derived from L1 sequences can cause suppression of L1 retrotransposition.

[39][38] Hypomethylation of a specific L1 located in the MET onco gene is associated with bladder cancer tumorogenesis,[40] Shift work sleep disorder[41] is associated with increased cancer risk because light exposure at night reduces melatonin, a hormone that has been shown to reduce L1-induced genome instability.

ORF2 protein (exhibiting reverse transcriptase and endonuclease activity) from human LINE-1 .
Genetic structure of murine LINE1 and SINEs . Bottom: proposed structure of L1 RNA-protein (RNP) complexes. ORF1 proteins form trimers, exhibiting RNA binding and nucleic acid chaperone activity.
Mechanism of target-primed reverse transcription (TPRT) , directly at the site of integration: L1 RNP recognize AAAATT hexanucleotides and ORF2 endonuclease activity cleaves the DNA first-strand. L1 polyA tail associate with TTTT overhang and the host DNA is used as a primer to initiate reverse-transcription. ORF2 probably also mediate second-strand cleavage and attachment of newly synthesized cDNA to the DNA template, using again host DNA as a primer for second-strand synthesis.