Fig. 1

Long terminal repeat (LTR) and non-LTR retrotransposition mechanisms. a Mammalian retrotransposon structures. A long interspersed element (LINE; human L1 shown) typically consists of a 5′ untranslated region (UTR; blue box) harboring an internal promoter, two open reading frames (ORF1, ORF2), a 3′ UTR (small blue box), and a poly(A)-tail. A short interspersed element (SINE; mouse B1 shown) does not encode proteins and is trans-mobilized by LINE proteins. An endogenous retrovirus (ERV), such as mouse intracisternal A-type particle (IAP) and Mus type-D related retrovirus (MusD), lacks an Env protein but encodes functional Gag and Pol proteins flanked by a LTR at the 5′ (black box) and 3′ (red box) ends. Arrows indicate transcription start sites. b ERV mobilization starts with mRNA transcription and translation to yield Gag and Gag–Pro–Pol fusion proteins. The fusion proteins consist of a Gag protein (Gag), a protease (Pr), an integrase (In), and a reverse transcriptase (RT). Gag proteins build a virus-like particle and encapsulate the fusion proteins, which are processed into separate mature proteins. The ERV mRNA is then reverse transcribed, generating a cDNA. This cDNA and the integrase build a preintegration complex. The integrase then creates a double-strand DNA break, followed by genomic integration of a new ERV copy. Target site duplications (TSDs) are indicated by blue triangles. c L1 mobilization begins with transcription of an L1 mRNA, which is translated to yield ORF1p and ORF2p. ORF1p, ORF2p, and the L1 mRNA form a ribonucleoprotein particle that re-enters the nucleus. The ORF2p endonuclease cleaves the first genomic DNA strand, while its reverse transcriptase uses a now free 3′ OH group as a primer for reverse transcription of the L1 mRNA. Following second-strand DNA cleavage, a new L1 copy is integrated into the genome and is typically flanked by TSDs