Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay
Standard
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.
in: PLOS ONE, Jahrgang 7, Nr. 2, 2012, S. e31363.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay
AU - Ochs, Meike J
AU - Sorg, Bernd L
AU - Pufahl, Laura
AU - Grez, Manuel
AU - Suess, Beatrix
AU - Steinhilber, Dieter
PY - 2012
Y1 - 2012
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.
AB - 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.
KW - Alternative Splicing/drug effects
KW - Arachidonate 5-Lipoxygenase/genetics
KW - Blotting, Western
KW - Calcitriol/pharmacology
KW - Cell Differentiation/drug effects
KW - Cell Line
KW - Gene Expression Regulation, Enzymologic/drug effects
KW - Gene Knockdown Techniques
KW - Humans
KW - Nonsense Mediated mRNA Decay/drug effects
KW - Puromycin/pharmacology
KW - RNA, Messenger/genetics
KW - Trans-Activators/metabolism
KW - Transcription, Genetic/drug effects
KW - Transforming Growth Factor beta1/pharmacology
U2 - 10.1371/journal.pone.0031363
DO - 10.1371/journal.pone.0031363
M3 - SCORING: Journal article
C2 - 22363630
VL - 7
SP - e31363
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 2
ER -
