title: Recurrent chimeric fusion RNAs in non-cancer tissues and cells.
abstract: Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of 'intergenic splicing'. We also explored the implications of these non-pathological fusions in cancer and in evolution.
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Babiceanu
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Fujun
authors.initials: F
authors.lastname: Qin
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Yuemeng
authors.initials: Y
authors.lastname: Jia
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lopez
authors.affiliation: Department of Computer Science, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Nick
authors.initials: N
authors.lastname: Janus
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Loryn
authors.initials: L
authors.lastname: Facemire
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Department of Computer Science, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
authors.forename: Iulia M
authors.initials: IM
authors.lastname: Lazar
authors.affiliation: Department of Pathology, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA hl9r@virginia.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D002461:Cell Line, Transformed; D019295:Computational Biology; D019143:Evolution, Molecular; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D050939:Gene Fusion; D015723:Gene Library; D020868:Gene Silencing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D061251:Primary Cell Culture; D012326:RNA Splicing; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013045:Species Specificity
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering
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