title: Exon-trapping mediated by the human retrotransposon SVA.
abstract: Although most human retrotransposons are inactive, both inactive and active retrotransposons drive genome evolution and may influence transcription through various mechanisms. In humans, three retrotransposon families are still active, but one of these, SVA, remains mysterious. Here we report the identification of a new subfamily of SVA, which apparently formed after an alternative splicing event where the first exon of the MAST2 gene spliced into an intronic SVA and subsequently retrotransposed. Additional examples of SVA retrotransposing upstream exons due to splicing into SVA were also identified in other primate genomes. After molecular and computational experiments, we found a number of functional 3' splice sites within many different transcribed SVAs across the human and chimpanzee genomes. Using a minigene splicing construct containing an SVA, we observed splicing in cell culture, along with SVA exonization events that introduced premature termination codons (PTCs). These data imply that an SVA residing within an intron in the same orientation as the gene may alter normal gene transcription either by gene-trapping or by introducing PTCs through exonization, possibly creating differences within and across species.
authors.affiliation: Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Dustin C
authors.initials: DC
authors.lastname: Hancks
authors.forename: Adam D
authors.initials: AD
authors.lastname: Ewing
authors.forename: Jesse E
authors.initials: JE
authors.lastname: Chen
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D005091:Exons / Q000235:genetics*; D020224:Expressed Sequence Tags; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011323:Primates / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D008869:Microtubule-Associated Proteins; D022821:RNA Splice Sites; D018626:Retroelements; D049452:Green Fluorescent Proteins; C503880:MAST2 protein, human; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C