Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia.
The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conse...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0128830 |
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| author | Jennifer Koenig Robert Werdehausen John E Linley Abdella M Habib Jeffrey Vernon Stephane Lolignier Niels Eijkelkamp Jing Zhao Andrei L Okorokov C Geoffrey Woods John N Wood James J Cox |
| author_facet | Jennifer Koenig Robert Werdehausen John E Linley Abdella M Habib Jeffrey Vernon Stephane Lolignier Niels Eijkelkamp Jing Zhao Andrei L Okorokov C Geoffrey Woods John N Wood James J Cox |
| author_sort | Jennifer Koenig |
| collection | DOAJ |
| description | The Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conserved in humans and mice. The NAT has a similar tissue expression pattern to the sense gene and is alternatively spliced within dorsal root ganglia. The human and mouse NATs exist in cis with the sense gene in a tail-to-tail orientation and both share sequences that are complementary to the terminal exon of SCN9A/Scn9a. Overexpression analyses of the human NAT in human embryonic kidney (HEK293A) and human neuroblastoma (SH-SY5Y) cell lines show that it can function to downregulate Nav1.7 mRNA, protein levels and currents. The NAT may play an important role in regulating human pain thresholds and is a potential candidate gene for individuals with chronic pain disorders that map to the SCN9A locus, such as Inherited Primary Erythromelalgia, Paroxysmal Extreme Pain Disorder and Painful Small Fibre Neuropathy, but who do not contain mutations in the sense gene. Our results strongly suggest the SCN9A NAT as a prime candidate for new therapies based upon augmentation of existing antisense RNAs in the treatment of chronic pain conditions in man. |
| format | Article |
| id | doaj-art-8a1eee2c1c6e4b68bfb0e8d73bdc021d |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-8a1eee2c1c6e4b68bfb0e8d73bdc021d2025-08-20T03:10:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e012883010.1371/journal.pone.0128830Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia.Jennifer KoenigRobert WerdehausenJohn E LinleyAbdella M HabibJeffrey VernonStephane LolignierNiels EijkelkampJing ZhaoAndrei L OkorokovC Geoffrey WoodsJohn N WoodJames J CoxThe Nav1.7 voltage-gated sodium channel, encoded by SCN9A, is critical for human pain perception yet the transcriptional and post-transcriptional mechanisms that regulate this gene are still incompletely understood. Here, we describe a novel natural antisense transcript (NAT) for SCN9A that is conserved in humans and mice. The NAT has a similar tissue expression pattern to the sense gene and is alternatively spliced within dorsal root ganglia. The human and mouse NATs exist in cis with the sense gene in a tail-to-tail orientation and both share sequences that are complementary to the terminal exon of SCN9A/Scn9a. Overexpression analyses of the human NAT in human embryonic kidney (HEK293A) and human neuroblastoma (SH-SY5Y) cell lines show that it can function to downregulate Nav1.7 mRNA, protein levels and currents. The NAT may play an important role in regulating human pain thresholds and is a potential candidate gene for individuals with chronic pain disorders that map to the SCN9A locus, such as Inherited Primary Erythromelalgia, Paroxysmal Extreme Pain Disorder and Painful Small Fibre Neuropathy, but who do not contain mutations in the sense gene. Our results strongly suggest the SCN9A NAT as a prime candidate for new therapies based upon augmentation of existing antisense RNAs in the treatment of chronic pain conditions in man.https://doi.org/10.1371/journal.pone.0128830 |
| spellingShingle | Jennifer Koenig Robert Werdehausen John E Linley Abdella M Habib Jeffrey Vernon Stephane Lolignier Niels Eijkelkamp Jing Zhao Andrei L Okorokov C Geoffrey Woods John N Wood James J Cox Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia. PLoS ONE |
| title | Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia. |
| title_full | Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia. |
| title_fullStr | Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia. |
| title_full_unstemmed | Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia. |
| title_short | Regulation of Nav1.7: A Conserved SCN9A Natural Antisense Transcript Expressed in Dorsal Root Ganglia. |
| title_sort | regulation of nav1 7 a conserved scn9a natural antisense transcript expressed in dorsal root ganglia |
| url | https://doi.org/10.1371/journal.pone.0128830 |
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