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Article Dans Une Revue Human Molecular Genetics Année : 2022

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

Franck Court
Yoan Renaud

Résumé

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.
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hal-03631345 , version 1 (05-04-2022)

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Marie-Elisa Pinson, Franck Court, Aymeric Masson, Yoan Renaud, Allison Fantini, et al.. L1 chimeric transcripts are expressed in healthy brain and their deregulation in glioma follows that of their host locus. Human Molecular Genetics, 2022, 31 (15), pp.2606-2622. ⟨10.1093/hmg/ddac056⟩. ⟨hal-03631345⟩
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