LINE elements propagate by a so-called target primed reverse transcription mechanism (TPRT), which was first described for the R2 element from the silkworm Bombyx mori.
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. The complex is transported back into the nucleus, where the ORF2 endonuclease domain opens the DNA (at TTAAAA hexanucleotide motifs in mammals). Thus, a 3'OH group is freed for the reverse transcriptase to prime reverse transcription of the LINE RNA transcript. Following the reverse transcription the target strand is cleaved and the newly created cDNA is integrated
New insertions create short target site duplications (TSDs), and the majority of new inserts are severely 5’-truncated (average insert size of 900bp in humans) and often inverted (Szak et al., 2002). Because they lack their 5’UTR, most of new inserts are non functional.