L1 chimeric transcripts are expressed in healthy brain and their deregulation in glioma follows that of their host locus.

Besides the consequences of retrotransposition, long interspersed element 1 (L1) retrotransposons can affect the host genome through their antisense promoter. In addition to the sense promoter, the evolutionarily recent L1 retrotransposons, which are present in several thousand copies, also possess an anti-sense promoter that can produce L1 chimeric transcripts (LCT) composed of the L1 5' UTR followed by the adjacent genomic sequence. The full extent to which LCT expression occurs in a given tissue and whether disruption of the defense mechanisms that normally control L1 retrotransposons affects their expression and function in cancer cells, remain to be established. By using CLIFinder, a dedicated bioinformatics tool, we found that LCT expression was widespread in normal brain and aggressive glioma samples, and that approximately 17% of recent L1 retrotransposons, from the L1PA1 to L1PA7 subfamilies, were involved in their production. Importantly, the transcriptional activities of the L1 antisense promoters and of their host loci were coupled. Accordingly, we detected LCT-producing L1 retrotransposons mainly in transcriptionally active genes and genomic loci. Moreover, changes in the host genomic locus expression level in glioma were associated with a similar change in LCT expression level, regardless of the L1 promoter methylation status. Our findings support a model in which the host genomic locus transcriptional activity is the main driving force of LCT expression. We hypothesize that this model is more applicable when host gene and LCT are transcribed from the same strand.

CLIFinder: identification of LINE-1 chimeric transcripts in RNA-seq data.

Summary: L1 Chimeric Transcripts (LCTs) are initiated by repeated LINE-1 element antisense promoters and include the L1 5'UTR sequence in antisense orientation followed by the adjacent genomic region. LCTs have been characterized mainly using bioinformatics approaches to query dbEST. To take advantage of NGS data to unravel the transcriptome composition, we developed Chimeric LIne Finder (CLIFinder), a new bioinformatics tool. Using stranded paired-end RNA-seq data, we demonstrated that CLIFinder can identify genome-wide transcribed chimera sequences corresponding to potential LCTs. Moreover, CLIFinder can be adapted to study transcription from other repeat types. Availability and implementation: The code is available at: https://github.com/GReD-Clermont/CLIFinder; and for Galaxy users, it is directly accessible in the tool shed at: https://toolshed.g2.bx.psu.edu/view/clifinder/clifinder/. Contact: catherine.barriere@uca.fr. Supplementary information: Supplementary data are available at Bioinformatics online.