title: The effects of retrotransposon-derived sequence insertions on gene expression in a model system.
abstract: Retrotransposition has been well documented as a significant source of mutagenesis in diverse eukaryotic organisms, including humans. Insertions of retrotransposons within or in close proximity to transcription units cause many spontaneous mutations, and have been implicated as a source of heritable genetic defects and as a cause of carcinogenesis. The mechanisms by which retrotransposon insertions produce mutant phenotypes are diverse and, in many cases, not fully understood. A model transcriptional system was utilized to test the effects of copia retrotransposon-derived sequence insertions upon gene expression in different cellular environments. The results of these experiments indicate that retrotransposon insertions within nontranslated regions of a transcription unit inhibit gene expression by at least two concurrently acting mechanisms: 1) transcriptional interference due to an active internal promoter and, 2) trans RNA hybridization interactions between transcripts containing complementary retrotransposon sequences.
authors.affiliation: Faculty of Biological Science, University of Tulsa, OK 74104.
authors.forename: S G
authors.initials: SG
authors.lastname: Wells
authors.forename: K S
authors.initials: KS
authors.lastname: Miller
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002457:Cell Extracts; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004251:DNA Transposable Elements; D004331:Drosophila melanogaster; D005091:Exons; D005786:Gene Expression Regulation; D019868:Kanamycin Kinase; D051379:Mice; D008957:Models, Genetic; D010770:Phosphotransferases / Q000378:metabolism; D010957:Plasmids; D016372:RNA, Antisense; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D002457:Cell Extracts; D004251:DNA Transposable Elements; D016372:RNA, Antisense; D015500:Chloramphenicol O-Acetyltransferase; D010770:Phosphotransferases; D019868:Kanamycin Kinase