title: Gene-breaking: a new paradigm for human retrotransposon-mediated gene evolution.
abstract: The L1 retrotransposon is the most highly successful autonomous retrotransposon in mammals. This prolific genome parasite may on occasion benefit its host through genome rearrangements or adjustments of host gene expression. In examining possible effects of L1 elements on host gene expression, we investigated whether a full-length L1 element inserted in the antisense orientation into an intron of a cellular gene may actually split the gene's transcript into two smaller transcripts: (1) a transcript containing the upstream exons and terminating in the major antisense polyadenylation site (MAPS) of the L1, and (2) a transcript derived from the L1 antisense promoter (ASP) that includes the downstream exons of the gene. Bioinformatic analysis and experimental follow-up provide evidence for this L1 "gene-breaking" hypothesis. We identified three human genes apparently "broken" by L1 elements, as well as 12 more candidate genes. Most of the inserted L1 elements in our 15 candidate genes predate the human/chimp divergence. If indeed split, the transcripts of these genes may in at least one case encode potentially interacting proteins, and in another case may encode novel proteins. Gene-breaking represents a new mechanism through which L1 elements remodel mammalian genomes.
authors: Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Sarah J
authors: SJ
authors: Wheelan
authors: Yasunori
authors: Y
authors: Aizawa
authors: Jeffrey S
authors: JS
authors: Han
authors: Jef D
authors: JD
authors: Boeke
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D019143:Evolution, Molecular; D005091:Exons; D020224:Expressed Sequence Tags; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D026723:Polyadenylation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D016375:Antisense Elements (Genetics); D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D018626:Retroelements; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met