The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference.

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The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference.
Piehler, Armin P; Hellum, Marit; Wenzel, Jürgen J; Kaminski, Ellen; Haug, Kari Bente Foss; Kierulf, Peter; Kaminski, Wolfgang E
BMC genomics 2008, 9:165

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dc.contributor.authorPiehler, Armin P-
dc.contributor.authorHellum, Marit-
dc.contributor.authorWenzel, Jürgen J-
dc.contributor.authorKaminski, Ellen-
dc.contributor.authorHaug, Kari Bente Foss-
dc.contributor.authorKierulf, Peter-
dc.contributor.authorKaminski, Wolfgang E-
dc.identifier.citationBMC genomics 2008, 9:165en
dc.description.abstractBACKGROUND: Pseudogenes are an integral component of the human genome. Little attention, however, has so far been paid to the phenomenon that some pseudogenes are transcriptionally active. Recently, we demonstrated that the human ortholog of the rodent testis-specific ATP-binding cassette (ABC) transporter Abca17 is a ubiquitously transcribed pseudogene (ABCA17P). The aim of the present study was to establish a complete inventory of all ABC transporter pseudogenes in the human genome and to identify transcriptionally active ABC transporter pseudogenes. Moreover, we tested the hypothesis that a regulatory interdependency exists between ABC transporter pseudogenes and their parental protein coding equivalents. RESULTS: Systematic bioinformatic analysis revealed the existence of 22 ABC transporter pseudogenes within the human genome. We identified two clusters on chromosomes 15 and 16, respectively, which harbor almost half of all pseudogenes (n = 10). Available information from EST and mRNA databases and RT-PCR expression profiling indicate that a large portion of the ABC transporter pseudogenes (45%, n = 10) are transcriptionally active and some of them are expressed as alternative splice variants. We demonstrate that both pseudogenes of the pseudoxanthoma elasticum gene ABCC6, ABCC6P1 and ABCC6P2, are transcribed. ABCC6P1 and ABCC6 possess near-identical promoter sequences and their tissue-specific expression profiles are strikingly similar raising the possibility that they form a gene-pseudogene dual transcription unit. Intriguingly, targeted knockdown of the transcribed pseudogene ABCC6P1 resulted in a significant reduction of ABCC6 mRNA expression levels. CONCLUSION: The human genome contains a surprisingly small number of ABC transporter pseudogenes relative to other known gene families. They are unevenly distributed across the chromosomes. Importantly, a significant portion of the ABC transporter pseudogenes is transcriptionally active. The downregulation of ABCC6 mRNA levels by targeted suppression of the expression of its pseudogene ABCC6P1 provides evidence, for the first time, for a regulatory interdependence of a transcribed pseudogene and its protein coding counterpart in the human genome.en
dc.publisherBioMed Centralen
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714en
dc.subject.meshATP-Binding Cassette Transportersen
dc.subject.meshBase Sequenceen
dc.subject.meshCell Lineen
dc.subject.meshComputational Biologyen
dc.subject.meshDNA Primersen
dc.subject.meshGene Expression Regulationen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshMultigene Familyen
dc.subject.meshRNA Interferenceen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshSequence Analysis, DNAen
dc.titleThe human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference.en
dc.typeJournal articleen
dc.typepeer revieweden
dc.contributor.departmentDepartment of Clinical Chemistry, Ulleval University Hospital, 0407 Oslo, Norway. armin.piehler@medisin.uio.noen
dc.contributor.departmentUllevaal University Hospitalen
dc.identifier.journalBMC genomicsen
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