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Human Dicer C-terminus functions as a 5-lipoxygenase binding domain

Biochimica et biophysica acta, 2009-02, Vol.1789 (2), p.99 [Peer Reviewed Journal]

ISSN: 0006-3002 ;EISSN: 1878-2434 ;DOI: 10.1016/j.bbagrm.2008.10.002 ;PMID: 19022417

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Title:
Human Dicer C-terminus functions as a 5-lipoxygenase binding domain
Author: Dincbas-Renqvist, Vildan ; Pépin, Geneviève ; Rakonjac, Marija ; Plante, Isabelle ; Ouellet, Dominique L ; Hermansson, Andreas ; Goulet, Isabelle ; Doucet, Johanne ; Samuelsson, Bengt ; Rådmark, Olof ; Provost, Patrick
Subjects: Arachidonate 5-Lipoxygenase - metabolism ; Cells, Cultured ; DEAD-box RNA Helicases - genetics ; DEAD-box RNA Helicases - metabolism ; Humans ; Immunoblotting ; Immunoprecipitation ; Medicin och hälsovetenskap ; Microscopy, Confocal ; Microscopy, Fluorescence ; Mutagenesis, Site-Directed ; Protein Binding - genetics ; Protein Structure, Tertiary - genetics ; Two-Hybrid System Techniques
Is Part Of: Biochimica et biophysica acta, 2009-02, Vol.1789 (2), p.99
Description: Dicer is a multidomain ribonuclease III enzyme involved in the biogenesis of microRNAs (miRNAs) in the vast majority of eukaryotes. In human, Dicer has been shown to interact with cellular proteins via its N-terminal domain. Here, we demonstrate the ability of Dicer C-terminus to interact with 5-lipoxygenase (5LO), an enzyme involved in the biosynthesis of inflammatory mediators, in vitro and in cultured human cells. Yeast two-hybrid and GST binding assays delineated the smallest 5-lipoxygenase binding domain (5LObd) of Dicer to its C-terminal 140 amino acids comprising the double-stranded RNA (dsRNA) binding domain (dsRBD). The Dicer 5LObd-5LO association was disrupted upon Ala substitution of Trp residues 13, 75 and 102 in 5LO, suggesting that the Dicer 5LObd may recognize 5LO via its N-terminal C2-like domain. Whereas a catalytically active 5LObd-containing Dicer fragment was found to enhance 5LO enzymatic activity in vitro, human 5LO modified the miRNA precursor processing activity of Dicer. Providing a link between miRNA-mediated regulation of gene expression and inflammation, our results suggest that the formation of miRNAs may be regulated by 5LO in leukocytes and cancer cells expressing this lipoxygenase.
Publisher: Netherlands
Language: English
Identifier: ISSN: 0006-3002
EISSN: 1878-2434
DOI: 10.1016/j.bbagrm.2008.10.002
PMID: 19022417
Source: SWEPUB Freely available online

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Human Dicer C-terminus functions as a 5-lipoxygenase binding domain

ISSN: 0006-3002 ;EISSN: 1878-2434 ;DOI: 10.1016/j.bbagrm.2008.10.002 ;PMID: 19022417

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