Mammalian LINE‐1 Retrotransposons and Related Elements

This chapter emphasises on the studies that have focused on understanding the mechanism of L1 retrotransposition, which were conducted since the publication of Mobile DNA in 1989. In addition, when appropriate the similarities and differences between the retrotransposition mechanisms of long interspersed nuclear elements (LINE-1s or L1s), closely related L1-like elements, and more distantly related non-LTR retrotransposons, are discussed. The majority of Cin4 elements are variably 5' truncated, rearranged, or mutated. The basic structural features of these nonautonomous retrotransposons are introduced in the chapter. The cultured cell assay also has yielded unexpected information about L1 retrotransposition. First, in cultured cells, 5 to 10% of new L1 retrotransposition events occurs into the introns of actively transcribed genes. Second, because L1s can be considered processed pseudogenes, the L1 pA signal lacks conserved elements that normally reside downstream of the poly(A) addition site in canonical RNA polymerase II pA signals. Finally, because most L1s are 5' truncated, it is possible that many transduction events are not detected because they completely lack L1 sequences. However, biochemical data argue that ORF1 binds particular A-rich sequences in L1 RNA with relatively high affinity and that ORF1p is more abundant than ORF2p. We just are beginning to realize the consequences of L1 retrotransposition on the human genome. Clearly, L1 is a mutagen. Moreover, because of the abundance of L1s, it is likely that L1s provide scaffolds for illegitimate recombination, which may contribute to the genome instability seen in many tumors.