Key role of the internal 5′-UTR segment in the transcription activity of the human L1 retrotransposon

The long 5′-untranslated region (5′-UTR) of the human L1 retrotransposon contains a unique internal promoter, allowing new L1 copies to be less dependent on the integration site at the transcriptional level. The mechanism of action of this promoter still remains unclear; however, some early studies have build up an opinion that the first 5′-UTR segment of 100–150 nt (known as the minimal promoter) is most crucial for the functioning of the full-length promoter. This study shows that the activity of the minimal promoter is rather low in comparison with the activity of the full-length 5′-UTR. Instead, 5′-UTR internal segment 390–662, containing numerous binding sites for various transcription factors, is indispensable for effective L1 transcription and can be considered as a transcriptional enhancer. Deletion of this segment dramatically reduces the level of transcription irrespective of the cell type, whereas deletion of the first 100 nt decreases the transcription level only by a factor of 1.5–2. Thus, the L1 regulatory region remains to be structurally similar to that of well-studied invertebrate LINEs. It is also possible that the internal 5′-UTR segment of L1 contains an alternative promoter, driving synthesis of a 5′-truncated L1 mRNA.