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

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 exp
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.
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Metadaten
Author:Meike Ochs, Bernd Lothar Sorg, Laura Pufahl, Manuel Grez, Beatrix Süß, Dieter Steinhilber
URN:urn:nbn:de:hebis:30:3-227807
DOI:http://dx.doi.org/doi:10.1371/journal.pone.0031363
ISSN:1932-6203
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=22363630
Parent Title (English):PLoS one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2012/01/09
Date of first Publication:2012/01/09
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2012/04/04
Volume:7
Issue:2: e31363
Pagenumber:8
HeBIS PPN:300355238
Institutes:Biochemie und Chemie
Biowissenschaften
Georg-Speyer-Haus
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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