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

PloS One
Meike J OchsDieter Steinhilber

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.

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R J BoadoK L Black
Jan 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R A DixonC A Rouzer
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Jan 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·M BrungsD Steinhilber
Dec 18, 2001·Nature Genetics·David BrettPeer Bork
Dec 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Benjamin P LewisSteven E Brenner
Jun 15, 2004·Current Opinion in Structural Biology·Liana F LareauSteven E Brenner
Sep 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Oliver WerzDieter Steinhilber
Feb 2, 2006·Molecular and Cellular Biology·Jürgen WittmannHans-Martin Jäck
Mar 17, 2007·The EMBO Journal·Wai-Kin ChanMiles F Wilkinson
Jun 20, 2007·Trends in Biochemical Sciences·Olof RådmarkBengt Samuelsson
Nov 26, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luc H BoudreauMarc E Surette

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Citations

Oct 8, 2013·PLoS Genetics·Meghan C Drummond, Karen H Friderici
May 7, 2013·Journal of Proteome Research·Meike J OchsPer-Johan Jakobsson
Aug 21, 2013·Wiley Interdisciplinary Reviews. RNA·Carol S Lutz, Ashley L Cornett
Nov 30, 2013·Basic & Clinical Pharmacology & Toxicology·Eeva Moilanen
Sep 12, 2013·Basic & Clinical Pharmacology & Toxicology·Meike J OchsDieter Steinhilber
Jun 13, 2015·AIDS Research and Human Retroviruses·Vincent MocquetPierre Jalinot
Mar 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Meike J SaulDieter Steinhilber
Jul 22, 2019·International Journal of Environmental Research and Public Health·Roger G Biringer
Feb 27, 2016·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Hsuan-Ni LinJ Patrick O'Connor
Sep 15, 2014·Molecular Biology Reports·Abhay Kumar SinghSharmistha Dey
Aug 6, 2019·Frontiers in Pharmacology·Meike J SaulBeatrix Suess

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Methods Mentioned

BETA
PCR
electrophoresis
Infrared Imaging

Software Mentioned

GraphPad Prism
BIO
ID

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