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Open Access Highly Accessed Research article

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

Armin P Piehler1*, Marit Hellum1, Jürgen J Wenzel2, Ellen Kaminski3, Kari Bente Foss Haug1, Peter Kierulf1 and Wolfgang E Kaminski4

Author Affiliations

1 Department of Clinical Chemistry, Ulleval University Hospital, 0407 Oslo, Norway

2 Institute for Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany

3 Department of Hygiene and Medical Microbiology, University of Heidelberg, 69120 Heidelberg, Germany

4 Institute for Clinical Chemistry, University of Heidelberg, 68167 Mannheim, Germany

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BMC Genomics 2008, 9:165  doi:10.1186/1471-2164-9-165

Published: 11 April 2008

Abstract

Background

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.