title: Arxes: retrotransposed genes required for adipogenesis.
abstract: Retrotransposed sequences arise from messenger RNAs (mRNAs) that have been reinserted into genomic DNA by reverse transcription. Usually, these sequences are embedded in dormant regions, collect missense mutations over time and constitute processed, nonfunctional pseudogenes. There are thousands of processed pseudogenes in the mouse and human genome. Here, we report evidence for two paralog genes (termed Arxes1 and Arxes2), which arose by retrotransposition of the signal peptidase Spcs3 followed by a segmental duplication event. They gained a functional promoter that we show to be transactivated by adipogenic transcription factors. We further show that the Arxes mRNAs are highly expressed in adipose tissue and strongly upregulated during adipogenesis in different cell models. Additionally, their expression is elevated by an anti-diabetic agent in vitro and in vivo. Importantly, we provide evidence that the Arxes genes are translated and that the proteins are located in the endoplasmic reticulum. Although the sequence similarity and subcellular location are reminiscent of their parental gene, our data suggest that the Arxes have developed a different function, since their expression is required for adipogenesis, whereas Spcs3 is dispensable. In summary, we report retrotransposed-duplicated genes that evolved from a parental gene to function in a tissue and adipogenesis-specific context.
authors.affiliation: Institute for Genomics and Bioinformatics, Graz University of Technology, Biocenter, Austria. andreas.prokesch@tugraz.at
authors.forename: Andreas
authors.initials: A
authors.lastname: Prokesch
authors.forename: Juliane G
authors.initials: JG
authors.lastname: Bogner-Strauss
authors.forename: Hubert
authors.initials: H
authors.lastname: Hackl
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rieder
authors.forename: Claudia
authors.initials: C
authors.lastname: Neuhold
authors.forename: Evelyn
authors.initials: E
authors.lastname: Walenta
authors.forename: Anne
authors.initials: A
authors.lastname: Krogsdam
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.forename: Christine
authors.initials: C
authors.lastname: Papak
authors.forename: Wing-Cheong
authors.initials: WC
authors.lastname: Wong
authors.forename: Charles
authors.initials: C
authors.lastname: Vinson
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D023281:Genomics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D047495:PPAR gamma / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D018626:Retroelements; D017422:Sequence Analysis, DNA; D015854:Up-Regulation
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D018626:Retroelements; C559257:Arxes1 protein, mouse; C559258:Arxes2 protein, mouse; D010447:Peptide Hydrolases