Recently active human retrotransposons (Long Terminal Repeat [LTR] and non-LTR groups) and their approximate representation in the human genome (in parentheses). While all sharing a polyA tail, the non-LTR retrotransposons are structurally distinct. The autonomous LINE-1 element (L1) contains two open reading frames while Alu and SVA do not. Alu is instead composed of two monomers linked by an A-rich linker sequence (A5TACA6). SVA is a composite element made up of a hexamer repeat of varying copy number, an Alu-like region, a region of variable numbers of tandem repeats, and an HERV-K derived region known as SINE-R. All non-LTR elements are flanked by target site duplications (arrows) that are typically between 5 and 10 bp. The only recently active LTR element in the human genome (HERV-K) has a distinct structure resembling most endogenous retroviruses—full-length copies contain a central region encoding the Gag, Pol, and Env proteins flanked by identical long terminal repeats and short TSDs. HERV-K was assayed only by Huang et al. (2010), exhibited relatively low insertion rates compared to non-LTR retrotransposons, and will not be mentioned further. L1, Alu, and SVA all mobilize via a mechanism known as TPRT (Target Primed Reverse Transcription; for review, see Ostertag and Kazazian 2001). During this process, the mobilizing element is transcribed via RNA pol II (LINE-1 and SVA) or RNA polIII (Alu). In the case of LINE-1, ORFs 1 and 2 are translated on the ribosomes and ORF1 will typically bind to its own transcript for transport back to the nucleus. Once in the nucleus, ORF1, which has endonuclease and reverse transcriptase activity, is responsible for creating and integrating a cDNA copy at some other location. Alu, and likely SVA elements, “hijack” the L1 enzymatic machinery, probably via docking to the ribosome, in order to facilitate their own nuclear reentry and reverse transcription (Boeke 1997; Ostertag et al. 2003).
