Translation of the Placenta Growth Factor mRNA is Severely Affected by a Small Open Reading Frame Localized in the 5′ Untranslated Region

Abstract

The recently identified placenta growth factor gene (PIGF) code for a protein related to the vascular permeability factor (VPF). We present evidence indicating that expression of this gene could be regulated at the post-transcriptional level. The region upstream to the coding region of P1GF mRNA contains a small open reading frame (ORF), potentially coding for a peptide of 15 amino acids. The translation of different constructs in reticulocyte and wheat germ lysates as well as in COS-1 and CV-1 cells indicates that this short region is a translational inhibitory element since mutations in its two potential initiator codons increase PIGF synthesis in vivo

Using RNAse protection assay, we demonstrate that the P1GF mRNAs obtained from human term placenta and JEG choriocarcinoma cell line have a complete 5′ untranslated region and, consequently, also the above mentioned small ORF.

Finally, the analysis of a bovine P1GF genomic clone reveals that this small ORF is strongly conserved with respect to both putative peptide sequences and distance from the PIGF coding region.

Key Words:

• angiogenesis
• growth factors
• translational regulation
• post-transcriptional regulation
• cancer
• human