Schematic representation of the genome organization of mammalian retroelements. LINE-1, RTE-1 (retrotransposable element-1), Alu (human SINE), and SVA form a group of non-LTR retroelements of which only LINE-1 and RTE-1 are autonomous (i.e., they produce proteins that are required for their retrotransposition); the rest of the members of this group parasitize LINE-1 retrotransposition machinery. LINE-1 elements are composed of the 5′ UTR that contains an internal RNA polymerase II (pol II) promoter (PRO) and two open reading frames (ORF1 and ORF2) that are separated in mouse and human L1s but are overlapping in the rat LINE-1. Adjacent to ORF2 is the 3′ UTR that contains a polyadenylation (pA) signal and ends in a stretch of adenine residues (pA tail) of variable length. The majority of the disease-causing L1 inserts contain rather long poly(A) tails. Gray arrows bordering each full-length element represent target-site duplications (TSD) that result from amplification of the integration site during each retrotransposition event. RTE elements contain a single ORF that encodes endonuclease and reverse transcriptase activities but in contrast to L1 ORF2 has no cis-domain. The RTE ORF is flanked by the 5′ and 3′ UTRs. Alu elements do not code for any proteins. They are driven by a RNA polymerase III promoter, shown as boxes A and B, contain a middle A-rich region (A), and end in a poly(A) tail. SVA elements are a recently discovered hominid-specific group of retroelements that are most likely transcribed by a pol II promoter. They contain a variable number of (CCCTCT) repeats followed by an Alu-like sequence, a VNTR region, and a sequence of retroviral origin (HERV-K) that was historically designated “SINE-R”; hence the name SVA. At the very 3′ end, SVA contains a poly(A) signal preceding a poly(A) tail. Little is known about their mechanism of mobility. ERVs are endogenous retroviruses that contain long terminal repeats (5′ and 3′LTRs) flanking sequences that produce proteins necessary for mobilization (gag, pol, env, etc.).
