| Autor: |
Li J; Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA, Laboratory of Molecular Technology, Advanced Technology Program, SAIC-Frederick, Inc., Frederick, MD 21702, USA, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA, Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA, Internal Medicine, The Ohio State University, Columbus, OH 43210, USA and Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA., Kannan M, Trivett AL, Liao H, Wu X, Akagi K, Symer DE |
| Abstrakt: |
Between 6 and 30% of human and mouse transcripts are initiated from transposable elements. However, the promoters driving such transcriptional activity are mostly unknown. We experimentally characterized an antisense (AS) promoter in mouse L1 retrotransposons for the first time, oriented antiparallel to the coding strand of L1 open reading frame-1. We found that AS transcription is mediated by RNA polymerase II. Rapid amplification of cDNA ends cloning mapped transcription start sites adjacent to the AS promoter. We identified >100 novel fusion transcripts, of which many were conserved across divergent mouse lineages, suggesting conservation of potential functions. To evaluate whether AS L1 transcription could regulate L1 retrotransposition, we replaced portions of native open reading frame-1 in donor elements by synonymously recoded sequences. The resulting L1 elements lacked AS promoter activity and retrotransposed more frequently than endogenous L1s. Overexpression of AS L1 transcripts also reduced L1 retrotransposition. This suppression of retrotransposition was largely independent of Dicer. Our experiments shed new light on how AS fusion transcripts are initiated from endogenous L1 elements across the mouse genome. Such AS transcription can contribute substantially both to natural transcriptional variation and to endogenous regulation of L1 retrotransposition. |
