A NOVEL HUMAN C-SIS MESSENGER-RNA SPECIES IS TRANSCRIBED FROM A PROMOTER IN C-SIS INTRON-1 AND CONTAINS THE CODE FOR AN ALTERNATIVE PDGF B-LIKE PROTEIN

The human platelet-derived growth factor (PDGF) B chain precursor is usually translated from a 3.5 kb c-sis/PDGF B gene transcript. The first exon of the c-sis gene contains the code for the signal peptide of the PDGF B chain precursor, preceded by a 1 kb long untranslated sequence with potent translation inhibitory activity, In this paper we show that a novel 2.6 kb c-sis mRNA present in the human choriocarcinoma cell line JEG-3 initiates at an alternative exon 1, which we refer to as exon 1a. The 90 bp long exon 1a is located in the center of the first intron of the gene. It coincides with a very pronounced DNase-l-hypersensitive site and is preceded by a functional promoter, Of the three ATG codons present in exon 1a, the third one perfectly matches the criteria of a consensus start codon. It initiates an open reading frame that is continuous with the code far the PDGF B chain precursor but lacks the code for a signal peptide, We conclude that this novel 2.6 kb c-sis mRNA species lacks the strong translation inhibitory potential of the regular exon 1 and contains the code for a PDGF B-like protein that may be targeted to the cell nucleus.