Translational regulation of platelet-derived growth factor B chain (c-sis)mRNA by short open reading frames in the 5 '-untranslated region

Platelet-derived growth factor B chain (PDGF-B/c-SIS), the product of c-sis proto-oncogene, is a potent mitogen and chemoattractant for cells of mesen chymal origin. Expression of PDGF-B/c-SIS is regulated at the translational level, in addition to at the transcriptional level. The 5'-untranslated re gion (5'-UTR) of PDCF-B/c-sis mRNA is known to inhibit translation of the d ownstream coding sequences, The 5'-UTR contains putative influential elemen ts, such as GC-rich elements, stem-loop structures and short open reading f rames (SORFs), To clarify the inhibition mechanism of PDGF-B/c-sis mRNA tra nslation, effects of three SORFs in the 5'-UTR on the translational regulat ion were investigated in transient expression assays. Introducing point mut ation(s) in the initiation codons of SORFs affected the reporter gene expre ssion in several cell lines (COS-1, U-2, JEG-3) Abrogation of three SORFs r esulted in an increase of the reporter gene expression both in beta-galacto sidase assay and Western blot analysis. These results suggest that SORFs in the 5'-UTR sequences have inhibitory effects on the translation of the dow nstream coding sequences.