Nucleic Acids Research, Vol 27, Issue 22 4517-4525, Copyright © 1999 by Oxford University Press
NA Timchenko, AL Welm, X Lu and LT Timchenko
The transcription factor CCAAT/enhancer binding protein beta, C/EBPbeta,
plays a significant role in the regulation of hepatocyte growth and
differentiation. A single mRNA coding for C/EBPbeta produces several
protein isoforms. Two pathways for generation of low molecular weight
C/EBPbeta isoforms have been described: specific proteolytic cleavage and
initiation of translation from different AUG codons of C/EBPbeta mRNA. A
truncated C/EBPbeta isoform, LIP, is induced in rat livers in response to
partial hepatectomy (PH) via the alternative translation mechanism. Here we
present evidence that CUG repeat binding protein, CUGBP1, interacts with
the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta
isoforms. Two binding sites for CUGBP1 are located side by side between the
first and second AUG codons of C/EBPbeta mRNA. One binding site is observed
in an out of frame short open reading frame (sORF) that has been previously
shown to regulate initiation of translation from different AUG codons of
C/EBPbeta mRNA. Analysis of cytoplasmic and polysomal proteins from rat
liver after PH showed that CUGBP1 is associated with polysomes that
translate low molecular weight isoforms of C/EBPbeta. The binding activity
of CUGBP1 to the 5' region of C/EBPbeta mRNA shows increased association
with these polysomal fractions after PH. Addition of CUGBP1 into a
cell-free translation system leads to increased translation of low
molecular weight isoforms of C/EBPbeta. Our data demonstrate that CUGBP1
protein is an important component for the regulation of initiation from
different AUG codons of C/EBPbeta mRNA.
ARTICLES
CUG repeat binding protein (CUGBP1) interacts with the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta isoforms
Huffington Center on Aging, Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA. nikolait@bcm.tmc.edu
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