Figure 1.

Retrotransposons in the human genome. (A) Shown are the sequence structures of transposable elements and their composition in the human genome. The LINE-1 retrotransposon encodes two proteins required for mobilization: ORF1p contains RNA binding properties, and ORF2p contains endonuclease (EN) and reverse transcriptase (RT) activities. Alu elements and SVAs are non-protein-coding retrotransposons and rely on LINE-1-encoded proteins for retrotransposition. Endogenous retroviruses (ERVs) and DNA transposons are no longer mobile in humans. However, our genome contains ERV copies that are transcriptionally active with partially intact open reading frames. (B) Shown is a diagram of the life cycle of LINE-1. In somatic cells, a full-length copy of LINE-1 escapes epigenetic silencing and is transcribed by RNA polymerase II. The LINE-1 RNA is translated into ORF1p and ORF2p, which together form ribonucleoproteins (RNPs) in cis. LINE-1-encoded proteins can also form RNPs in trans with other transcripts, including Alu elements and SVAs. LINE-1 RNPs are commonly found in cytosolic aggregates, which are poorly characterized. Once RNPs access the nucleus, LINE-1 retrotransposition is initiated by ORF2p via target-primed reverse transcription to generate a new copy of the element in the genome. Alternatively, LINE-1 retrotransposition can be a source of DNA damage and genome instability.