Conserved 3′ UTR stem-loop structure in L1 and Alu transposons in human genome: possible role in retrotransposition

Daria Grechishnikova, Maria Poptsova

In the process of retrotransposition LINEs use their own machinery for copying and inserting themselves into new genomic locations, while SINEs are parasitic and require the machinery of LINEs. The exact mechanism of how a LINE-encoded reverse transcriptase (RT) recognizes its own and SINE RNA remains unclear. However it was shown for the stringent-type LINEs that recognition of a stem-loop at the 3'UTR by RT is essential for retrotransposition. For the relaxed-type LINEs it is believed that the poly-A tail is a common recognition element between LINE and SINE RNA. However polyadenylation is a property of any messenger RNA, and how the LINE RT recognizes transposon and non-transposon RNAs remains an open question. It is likely that RNA secondary structures play an important role in RNA recognition by LINE encoded proteins. Here we selected a set of L1 and Alu elements from the human genome and investigated their sequences for the presence of position-specific stem-loop structures. We found highly conserved stem-loop positions at the 3'UTR. Comparative structural analyses of a human L1 3'UTR stem-loop showed a similarity to 3'UTR stem-loops of the stringent-type LINEs, which were experimentally shown to be recognized by LINE RT. The consensus stem-loop structure consists of 5-7 bp loop, 8-10 bp stem with a bulge at a distance of 4-6 bp from the loop. The results show that a stem loop with a bulge exists at the 3'-end of Alu. We also found conserved stem-loop positions at 5'UTR and at the end of ORF2 and discuss their possible role. Here we presented an evidence for the presence of a highly conserved 3'UTR stem-loop structure in L1 and Alu retrotransposons in the human genome. Both stem-loops show structural similarity to the stem-loops of the stringent-type LINEs experimentally confirmed as essential for retrotransposition. Here we hypothesize that both L1 and Alu RNA are recognized by L1 RT via the 3'-end RNA stem-loop structure. Other conserved stem-loop positions in L1 suggest their possible functions in protein-RNA interactions but to date no experimental evidence has been reported.