Fig. 1
From: L1 retrotransposition in the soma: a field jumping ahead
L1 retrotransposon structure and mobilization scenarios. a. A human L1-Ta element (top) is 6 kb in length and encodes two protein-coding open reading frames (ORF1 and ORF2) flanked by 5′ and 3′ UTRs. New L1 insertions are typically flanked by a 3′ polyadenine (An) tract as mRNA polyadenylation is critical to efficient L1 retrotransposition [61, 62]. An antisense open reading frame (ORF0, brown rectangle) is located in the 5′UTR and may facilitate retrotransposition [209]. ORF2p possesses endonuclease (EN) and reverse transcriptase (RT) activities [44, 45]. The L1 is transcribed from 5′ sense (canonical) [47] and antisense [208] promoters, as indicated by black arrows. Target-primed reverse transcription (TPRT) typically generates short target site duplications (TSDs, indicated by red triangles) flanking new L1 insertions [44, 46, 64, 66]. A closer view of the L1 5′UTR (bottom) indicates YY1 (purple rectangle), RUNX (brown rectangle) and SRY family (e.g. SOX2, pink rectangle) transcription factor binding sites [22, 69, 207]. Numerous CpG dinucleotides (orange bars) occur throughout this region and, at a point of sufficient density, form a CpG island (green line) that is regulated by a complex including MeCP2, HDAC1 and HDAC2 [27, 47, 75, 105]. b. Example L1 mobilization scenarios. Top: A donor L1 is transcribed from its canonical promoter, generates a polyadenylated mRNA, and is retrotransposed via TPRT, generating a new L1 insertion that is 5′ truncated. Middle: Transcription initiated by a promoter upstream of the donor L1 reads through into the L1 and generates a spliced (dotted line) mRNA. As a result, the new L1 insertion carries a 5′ transduction. Bottom: Transcription initiates as directed by the canonical promoter but reads through the L1 polyA signal to an alternative downstream signal. Reverse transcription and integration of this mRNA generates a 5′ truncated L1 insertion flanked by a 3′ transduction. Note: the monomeric promoters of the active mouse L1 subfamilies (TF, GF, A) are very different in their structure, and potentially their regulation, than the human L1-Ta promoter. Aspects of the figure are adapted from previous works [35, 290]