Full-Length Human L1 Insertions Retain the Capacity for High Frequency Retrotransposition in Cultured Cells

Abstract

Functional L1 elements are autonomous retrotransposons that can insert into human genes and cause disease. To date, 10 of 12 known L1 retrotranspositions into human genes have been found to be 5′-truncated and incapable of further retrotransposition. Here we report the nucleotide sequences of the two full-length L1 elements, L1_β-thal and L1_RP, that have inserted into the β-globin and retinitis pigmentosa-2 (RP2) genes, respectively. L1_β-thal is 99.4% identical to a consensus sequence of active human L1s, while L1_RP is 99.9% identical. Both elements retain impressive capacity for high frequency retro-transposition in cultured HeLa cells. Indeed, L1_RP is the most active L1 isolated to date. Our data indicate that not all L1 insertions into human genes are ‘dead on arrival’. Our findings also lend further credence to the concept of cis preference, that the proteins encoded by a particular L1 preferentially act upon their encoding RNA as opposed to other L1 RNAs.