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Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay.

Ochs, Meike J. ; Sorg, Bernd L. ; Pufahl, Laura ; Grez, Manuel ; Suess, Beatrix ; Steinhilber, Dieter (2012)
Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay.
In: PloS one, 7 (2)
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of leukotrienes (LT), a group of inflammatory lipid mediators derived from arachidonic acid. Here, we investigated the regulation of 5-LO mRNA expression by alternative splicing and nonsense-mediated mRNA decay (NMD). In the present study, we report the identification of 2 truncated transcripts and 4 novel 5-LO splice variants containing premature termination codons (PTC). The characterization of one of the splice variants, 5-LOΔ3, revealed that it is a target for NMD since knockdown of the NMD factors UPF1, UPF2 and UPF3b in the human monocytic cell line Mono Mac 6 (MM6) altered the expression of 5-LOΔ3 mRNA up to 2-fold in a cell differentiation-dependent manner suggesting that cell differentiation alters the composition or function of the NMD complex. In contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown. Thus, the data suggest that the coupling of alternative splicing and NMD is involved in the regulation of 5-LO gene expression.

Typ des Eintrags: Artikel
Erschienen: 2012
Autor(en): Ochs, Meike J. ; Sorg, Bernd L. ; Pufahl, Laura ; Grez, Manuel ; Suess, Beatrix ; Steinhilber, Dieter
Art des Eintrags: Bibliographie
Titel: Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay.
Sprache: Englisch
Publikationsjahr: 2012
Titel der Zeitschrift, Zeitung oder Schriftenreihe: PloS one
Jahrgang/Volume einer Zeitschrift: 7
(Heft-)Nummer: 2
Kurzbeschreibung (Abstract):

5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of leukotrienes (LT), a group of inflammatory lipid mediators derived from arachidonic acid. Here, we investigated the regulation of 5-LO mRNA expression by alternative splicing and nonsense-mediated mRNA decay (NMD). In the present study, we report the identification of 2 truncated transcripts and 4 novel 5-LO splice variants containing premature termination codons (PTC). The characterization of one of the splice variants, 5-LOΔ3, revealed that it is a target for NMD since knockdown of the NMD factors UPF1, UPF2 and UPF3b in the human monocytic cell line Mono Mac 6 (MM6) altered the expression of 5-LOΔ3 mRNA up to 2-fold in a cell differentiation-dependent manner suggesting that cell differentiation alters the composition or function of the NMD complex. In contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown. Thus, the data suggest that the coupling of alternative splicing and NMD is involved in the regulation of 5-LO gene expression.

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie > Synthetic Genetic Circuits (2020 umbenannt in "Synthetic RNA biology")
10 Fachbereich Biologie
Hinterlegungsdatum: 12 Mär 2012 12:50
Letzte Änderung: 05 Mär 2013 09:59
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