Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.

Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.

Nicotinic acetylcholine receptor subunits (nAChR) are associated with different aspects of smoking behaviour as well as with smoking related disorders. Several of these subunits have been found to be upregulated in smokers or differentially expressed in lung tumor cells. The mechanisms behind these...

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Autores principales: Marlene Eggert, Eric Aichinger, Michael W Pfaffl, Ortrud K Steinlein, Martina Pfob
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/38391d1efc3e4c5a8cd5ac6fcf259b1b
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spelling oai:doaj.org-article:38391d1efc3e4c5a8cd5ac6fcf259b1b2021-11-18T07:39:11ZNicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.1932-620310.1371/journal.pone.0066157https://doaj.org/article/38391d1efc3e4c5a8cd5ac6fcf259b1b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23843950/?tool=EBIhttps://doaj.org/toc/1932-6203Nicotinic acetylcholine receptor subunits (nAChR) are associated with different aspects of smoking behaviour as well as with smoking related disorders. Several of these subunits have been found to be upregulated in smokers or differentially expressed in lung tumor cells. The mechanisms behind these observations are not known but assumed to be mainly post-transcriptional. Many post-transcriptional mechanisms are initiated by functionally relevant sequence motifs within untranslated gene regions, such as upstream open reading frames (uORFs). We performed a systematic search in all smoking-associated neuronal nAChR subunits and identified functionally relevant uORFs in CHRNA4 and CHRNA5. Luciferase experiments showed that these uORFs are able to significantly decrease protein expression. Our quantitative real-time PCR (qPCR) results strongly suggest that the observed effects originate at the translation rather than at the transcription level. Interestingly, the CHRNA4 uORF was only functionally relevant when expressed in the shorter isoform of this gene. Therefore, the data presented in this study strongly points towards an important role of uORFs within the 5'UTR of CHRNA4-isoform 1 and CHRNA5 as regulators of protein translation. Moreover, the shared uORF of CHRNA4-isoform 1/isoform 2 represents the first example of a sequence context-dependent uORF.Marlene EggertEric AichingerMichael W PfafflOrtrud K SteinleinMartina PfobPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e66157 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marlene Eggert
Eric Aichinger
Michael W Pfaffl
Ortrud K Steinlein
Martina Pfob
Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
description Nicotinic acetylcholine receptor subunits (nAChR) are associated with different aspects of smoking behaviour as well as with smoking related disorders. Several of these subunits have been found to be upregulated in smokers or differentially expressed in lung tumor cells. The mechanisms behind these observations are not known but assumed to be mainly post-transcriptional. Many post-transcriptional mechanisms are initiated by functionally relevant sequence motifs within untranslated gene regions, such as upstream open reading frames (uORFs). We performed a systematic search in all smoking-associated neuronal nAChR subunits and identified functionally relevant uORFs in CHRNA4 and CHRNA5. Luciferase experiments showed that these uORFs are able to significantly decrease protein expression. Our quantitative real-time PCR (qPCR) results strongly suggest that the observed effects originate at the translation rather than at the transcription level. Interestingly, the CHRNA4 uORF was only functionally relevant when expressed in the shorter isoform of this gene. Therefore, the data presented in this study strongly points towards an important role of uORFs within the 5'UTR of CHRNA4-isoform 1 and CHRNA5 as regulators of protein translation. Moreover, the shared uORF of CHRNA4-isoform 1/isoform 2 represents the first example of a sequence context-dependent uORF.
format article
author Marlene Eggert
Eric Aichinger
Michael W Pfaffl
Ortrud K Steinlein
Martina Pfob
author_facet Marlene Eggert
Eric Aichinger
Michael W Pfaffl
Ortrud K Steinlein
Martina Pfob
author_sort Marlene Eggert
title Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
title_short Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
title_full Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
title_fullStr Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
title_full_unstemmed Nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
title_sort nicotinic acetylcholine receptor subunits α4 and α5 associated with smoking behaviour and lung cancer are regulated by upstream open reading frames.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/38391d1efc3e4c5a8cd5ac6fcf259b1b
work_keys_str_mv AT marleneeggert nicotinicacetylcholinereceptorsubunitsa4anda5associatedwithsmokingbehaviourandlungcancerareregulatedbyupstreamopenreadingframes
AT ericaichinger nicotinicacetylcholinereceptorsubunitsa4anda5associatedwithsmokingbehaviourandlungcancerareregulatedbyupstreamopenreadingframes
AT michaelwpfaffl nicotinicacetylcholinereceptorsubunitsa4anda5associatedwithsmokingbehaviourandlungcancerareregulatedbyupstreamopenreadingframes
AT ortrudksteinlein nicotinicacetylcholinereceptorsubunitsa4anda5associatedwithsmokingbehaviourandlungcancerareregulatedbyupstreamopenreadingframes
AT martinapfob nicotinicacetylcholinereceptorsubunitsa4anda5associatedwithsmokingbehaviourandlungcancerareregulatedbyupstreamopenreadingframes
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