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

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) tran...

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Autores principales: Piehler, Armin P, Hellum, Marit, Wenzel, Jürgen J, Kaminski, Ellen, Haug, Kari Bente Foss, Kierulf, Peter, Kaminski, Wolfgang E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2329642/
https://www.ncbi.nlm.nih.gov/pubmed/18405356
http://dx.doi.org/10.1186/1471-2164-9-165
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author Piehler, Armin P
Hellum, Marit
Wenzel, Jürgen J
Kaminski, Ellen
Haug, Kari Bente Foss
Kierulf, Peter
Kaminski, Wolfgang E
author_facet Piehler, Armin P
Hellum, Marit
Wenzel, Jürgen J
Kaminski, Ellen
Haug, Kari Bente Foss
Kierulf, Peter
Kaminski, Wolfgang E
author_sort Piehler, Armin P
collection PubMed
description 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.
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spelling pubmed-23296422008-04-23 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 Research Article 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. BioMed Central 2008-04-11 /pmc/articles/PMC2329642/ /pubmed/18405356 http://dx.doi.org/10.1186/1471-2164-9-165 Text en Copyright © 2008 Piehler et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Piehler, Armin P
Hellum, Marit
Wenzel, Jürgen J
Kaminski, Ellen
Haug, Kari Bente Foss
Kierulf, Peter
Kaminski, Wolfgang E
The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference
title The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference
title_full The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference
title_fullStr The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference
title_full_unstemmed The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference
title_short The human ABC transporter pseudogene family: Evidence for transcription and gene-pseudogene interference
title_sort human abc transporter pseudogene family: evidence for transcription and gene-pseudogene interference
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2329642/
https://www.ncbi.nlm.nih.gov/pubmed/18405356
http://dx.doi.org/10.1186/1471-2164-9-165
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