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Nucleic Acids Research, 1995, Vol. 23, No. 15 2815-2822
© 1995

MOLECULAR BIOLOGY

A novel human c-sis mRNA species is transcribed from a promoter in c-sis intron 1 and contains the code for an alternative PDGF B-like protein

Ron P.H. Dirks*, Carla Onnekink, Hans J. Jansen, Aard de Jong and Henri P.J. Bloemers

Department of Biochemistry, University of Nijmegen PO Box 9101, 6500 HB Nijmegen, The Netherlands

*To whom correspondence should be addressed at present address: Department of Molecular Biology, University of Nijmegen, Toernooiveld , 6525 ED Nijmegen, The Netherlands

Received June 1, 1995. Accepted June 26, 1995.

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-hhypersensitive site and is preceded by a functional promoter. Of the three ATG codons present in exon 1 a, the third one perfectly matches the criteria of a consensus start codon. It Initiates an open reading frame that is continuous with the code for 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-IIke protein that may be targeted to the cell nucleus.


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