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

Authors: Dincbas-Renqvist, Vildan; Pépin, Geneviève; Rakonjac, Marija; Plante, IsabelleOuellet, Dominique; Hermansson, Andreas; Goulet, IsabelleDoucet, Johanne; Samuelsson, Bengt; Rådmark, Olof; Provost, Patrick
Abstract: 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.
Document Type: Article de recherche
Issue Date: 1 February 2009
Open Access Date: Restricted access
Document version: VoR
This document was published in: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Vol. 1789, 99-108 (2009)
Alternative version: 10.1016/j.bbagrm.2008.10.002
Collection:Articles publiés dans des revues avec comité de lecture

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