PDGF2/c-sis mRNA leader contains a differentiation-linked internal ribosomal entry site (D-IRES).
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'-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.
Bernstein
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Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Sella
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Elroy-Stein
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D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics*
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases