Figure 1. Simplified schematic of the proposed mechanism of L1 retrotransposition. (1) A full-length active L1 element in the genome is first transcribed using an internal promoter. (2) The L1 transcript is exported to the nucleus. (3) The ORF1 and ORF2 proteins are translated and preferentially bind the RNA molecule that encoded them (cis preference). (4) The L1 RNA and associated protein(s) return to the nucleus by active transport or entry during nuclear membrane breakdown at mitosis. (5) The L1 RNA is reverse transcribed and integrated into the genome by target primed reverse transcription (TPRT). The process depicted results in a DNA copy of the original L1 element at a new genomic location. Note that the target site duplications flanking the original L1 element (represented by black rectangles) will differ from the target site duplications flanking the L1 copy at a new genomic location (represented by shaded rectangles). The new L1 copy also often differs from the original by truncating or rearranging during the retrotransposition process.
Figure 2. Target primed reverse transcription (TPRT). The L1 retrotransposon is thought to integrate by TPRT. (1) During L1 TPRT, the retrotransposon's endonuclease cleaves one strand of genomic DNA at its target site (rectangle), producing a 3′ hydroxyl (OH) at the nick. (2) The retrotransposon RNA hybridizes at the nick. (3) The retrotransposon's reverse transcriptase uses the free 3′ OH to prime reverse transcription. Reverse transcription proceeds, producing a cDNA of the retrotransposon RNA. (4) The endonuclease cleaves the second DNA strand of the target site to produce a staggered break. (5) The cDNA inserts into the break by an unknown mechanism. (6) Removal of RNA and completion of DNA synthesis produces a complete insertion flanked by target site duplications (TSDs).