TY  - JOUR
A1  - Ochs, Meike
A1  - Sorg, Bernd Lothar
A1  - Pufahl, Laura
A1  - Grez, Manuel
A1  - Süß, Beatrix
A1  - Steinhilber, Dieter
T1  - Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay
T2  - PLoS One
N2  - 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.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22780
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-227807
SN  - 1932-6203
VL  - 7
IS  - 2: e31363
PB  - PLoS
CY  - Lawrence, Kan.
ER  -