Non-LTR retrotransposons are a type of class I transposons that currently account for approximately 17% of the human genome. Unlike LTR retrotransposons with their characteristic long terminal repeats, non-LTR retrotransposons gain their name from the lack of these motifs. Non-LTR retrotransposons themselves are subdivided into two categories - Long Interspersed Nuclear Elements, or LINEs, and Short Interspersed Nuclear Elements, or SINEs.

While LINEs are autonomous and can encode proteins essential for their mobilization, SINEs are non-autonomous retrotransposons and require proteins encoded by other elements for their mobilization. For example, L1 elements - a type of LINE retrotransposon and one of the few autonomous transposons active in humans - are approximately 6kb long elements containing two open reading frames. ORF1 encodes for a protein with RNA binding and chaperone activities. ORF2 encodes for a protein with reverse transcriptase and endonuclease domains.

Both of these proteins are essential for the mobilization of the L1 element. Inside the nucleus, the RNA polymerase II first transcribes the L1 element into an L1 RNA, which is then polyadenylated and transported to the cytoplasm to be translated into ORF1 and ORF2 proteins. Both of these proteins then associate with the L1 RNA to form an L1 ribonucleoprotein, or RNP. The L1 RNP is imported back into the nucleus where it uses its endonuclease activity to make staggered nicks at the AT rich target site.

The reverse transcriptase then uses the loose 3’ end of one of the DNA strands as the primer for reverse transcription of the L1 RNA. This process is called target-site primed reverse transcription. The L1 RNA is then digested while a cellular DNA polymerase starts extending the 3’ OH end of the complementary DNA strand using the newly synthesized DNA strand as the template. Finally, the ends of the newly synthesized L1 element are sealed by the host enzymes - resulting in target site duplication.

In contrast to LINEs, SINEs are only around 100-400 bp in length and cannot encode proteins required for their transposition. However, most SINE elements contain structural features such as a 3’ AT-rich sequence that upon transcription enables them to be recognized by the LINE encoded proteins. This facilitates their integration into the genome via the same nick-and-copy process as LINE elements.