Figure 4. A model for A3A-mediated inhibition of L1 retrotransposition.
The left side of the Figure shows L1 integration reactions that occur via TPRT. The right side of the Figure shows the predicted structures of the resultant L1 retrotransposition events. Shown are transiently exposed single-strand genomic DNA regions that ultimately give rise to target site duplications (TSDs: orange lines), the L1 RNA (red line), the L1 cDNA (blue line), and the A3A protein (green oval). UGI expression (red stop sign) can inhibit UNG activity. (A) Deamination of the L1 cDNA: in the presence of cellular RNase H, A3A-mediated deamination of the L1 (−) strand cDNA (blue lettering) in the presence of UGI leads to C-to-T mutations on the L1 non-coding strand and G-to-A mutations on the L1 (+) coding strand. (B) Deamination of the 5′ flanking top-strand genomic DNA: in the presence of UGI, deamination of the transiently exposed single-strand 5′ flanking genomic DNA (top orange line) during TPRT results in C-to-T changes in the 5′ TSD relative to the 3′ TSD. (C) Deamination of the 3′ flanking bottom-strand genomic DNA: in the presence of UGI, deamination of transiently exposed single-strand 3′ flanking genomic DNA during TPRT, in principle, is predicted to result in a G-to-A change in the 3′ TSD relative to the 5′ TSD.