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

PLoS One. 2012;7(2):e31363. doi: 10.1371/journal.pone.0031363. Epub 2012 Feb 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects
  • Alternative Splicing / genetics*
  • Arachidonate 5-Lipoxygenase / genetics*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Blotting, Western
  • Calcitriol / pharmacology
  • Cell Differentiation / drug effects
  • Cell Line
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Nonsense Mediated mRNA Decay / drug effects
  • Nonsense Mediated mRNA Decay / genetics*
  • Puromycin / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trans-Activators / metabolism
  • Transcription, Genetic* / drug effects
  • Transforming Growth Factor beta1 / pharmacology


  • RNA, Messenger
  • Trans-Activators
  • Transforming Growth Factor beta1
  • Puromycin
  • Arachidonate 5-Lipoxygenase
  • Calcitriol