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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2014 ; 289
(38
): 26226-26238
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The RNA-editing enzyme APOBEC1 requires heterogeneous nuclear ribonucleoprotein Q
isoform 6 for efficient interaction with interleukin-8 mRNA
#MMPMID25100733
Shimizu Y
; Nishitsuji H
; Marusawa H
; Ujino S
; Takaku H
; Shimotohno K
J Biol Chem
2014[Sep]; 289
(38
): 26226-26238
PMID25100733
show ga
Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide 1 (APOBEC1) is an
intestine-specific RNA-binding protein. However, inflammation or exposure to
DNA-damaging agents can induce ectopic APOBEC1 expression, which can result in
hepatocellular hyperplasia in animal models. To identify its RNA targets,
FLAG-tagged APOBEC1 was immunoprecipitated from transfected HuH7.5 hepatocellular
carcinoma cells and analyzed using DNA microarrays. The interleukin-8 (IL8) mRNA
was the most abundant co-precipitated RNA. Exogenous APOBEC1 expression increased
IL8 production by extending the half-life of the IL8 mRNA. A cluster of AU-rich
elements in the 3'-UTR of IL8 was essential to the APOBEC1-mediated increase in
IL8 production. Notably, IL8 mRNA did not co-immunoprecipitate with APOBEC1 from
lysates of other cell types at appreciable levels; therefore, other factors may
enhance the association between APOBEC1 and IL8 mRNA in a cell type-specific
manner. A yeast two-hybrid analysis and siRNA screen were used to identify
proteins that enhance the interaction between APOBEC1 and IL8 mRNA. Heterogeneous
nuclear ribonucleoprotein Q (hnRNPQ) was essential to the APOBEC1/IL8 mRNA
association in HuH7.5 cells. Of the seven hnRNPQ isoforms, only hnRNPQ6 enabled
APOBEC1 to bind to IL8 mRNA when overexpressed in HEK293 cells, which expressed
the lowest level of endogenous hnRNPQ6 among the cell types examined. The results
of a reporter assay using a luciferase gene fused to the IL8 3'-UTR were
consistent with the hypothesis that hnRNPQ6 is required for APOBEC1-enhanced IL8
production. Collectively, these data indicate that hnRNPQ6 promotes the
interaction of APOBEC1 with IL8 mRNA and the subsequent increase in IL8
production.