title: The 5' untranslated sequence of the c-sis/platelet-derived growth factor 2 transcript is a potent translational inhibitor.
abstract: c-sis/platelet-derived growth factor 2 (PDGF-2) is a prototype growth factor with transforming potential. The c-sis/PDGF-2 transcript contains a long 5' untranslated sequence (UTS) that is highly G.C rich. To examine the influence of this sequence on sis/PDGF-2 expression, we localized the c-sis/PDGF-2 promoter and used this promoter or the simian virus 40 early promoter to drive expression of the bacterial chloramphenicol acetyltransferase or sis/PDGF-2 gene. The 5' UTS of c-sis/PDGF-2 mRNA had no effect on RNA expression but was shown to exert a potent inhibitory effect on translation. By deletion analysis, we demonstrated that the 5' UTS inhibited protein expression by as much as 40-fold. The inhibitory effect was independent of reporter gene, cell type, or promoter used. A highly G.C-rich 140-base-pair sequence immediately preceding the c-sis/PDGF-2 initiation codon was shown to be nearly as effective as the entire 5' UTS in translational inhibition. Transfection analysis demonstrated that the 5' UTS significantly reduced the transforming efficiency of the sis/PDGF-2 gene as well. Thus, our findings raise the possibility that changes in regulation at the level of sis/PDGF-2 translation may play a role in development of the neoplastic phenotype.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: C D
authors.initials: CD
authors.lastname: Rao
authors.forename: M
authors.initials: M
authors.lastname: Pech
authors.forename: K C
authors.initials: KC
authors.lastname: Robbins
authors.forename: S A
authors.initials: SA
authors.lastname: Aaronson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005786:Gene Expression Regulation; D006860:Hydrogen Bonding; D009690:Nucleic Acid Conformation; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger