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(Received for publication, November 15, 1996)
From the It has become clear that a given cell type can
qualitatively and quantitatively affect the expression of the
platelet-derived growth factor B (PDGF2/c-sis) gene at
multiple levels. In a previous report, we showed that
PDGF2/c-sis 5
Volume 272, Number 14,
Issue of April 4, 1997
pp. 9356-9362
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
Department of Cell Research and Immunology,
George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv
69978, Israel and the § Laboratory of Mathematical Biology,
DCBDC, NCI, NIH, Frederick, Maryland 21702
-untranslated region has a translational
modulating activity during megakaryocytic differentiation of K562
cells. This study points to the mechanism used for this translational
modulation. The unusual mRNA leader, which imposes a major barrier
to conventional ribosomal scanning, was found to contain an internal
ribosomal entry site that becomes more potent in differentiating cells
and was termed differentiation-linked internal ribosomal entry site
(D-IRES). The D-IRES element defines a functional role for the
cumbersome 1022-nucleotide-long mRNA leader and accounts for its
uncommon, evolutionary conserved architecture. The
differentiation-linked enhancement of internal translation, which
provides an additional step to the fine tuning of
PDGF2/c-sis gene expression, might be employed by numerous
critical regulatory genes with unusual mRNA leaders and might have
widespread implications for cellular growth and development.
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I. Stein, A. Itin, P. Einat, R. Skaliter, Z. Grossman, and E. Keshet Translation of Vascular Endothelial Growth Factor mRNA by Internal Ribosome Entry: Implications for Translation under Hypoxia Mol. Cell. Biol., June 1, 1998; 18(6): 3112 - 3119. [Abstract] [Full Text]
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