NORMAL DEVELOPING RAT-BRAIN EXPRESSES A PLATELET-DERIVED GROWTH-FACTOR-B CHAIN (C-SIS) MESSENGER-RNA TRUNCATED AT THE 5' END

The 5' untranslated sequence (5' UTS) of platelet-derived growth facto r B (PDGF-B/c-sis) mRNA is highly preserved through evolution, and inh ibits translation of downstream coding sequences, In this study, using Northern analysis we identified two PDGF-B/c-sis mRNAs (3.5 kb and 2. 6 kb) expressed in normal developing rat brain. In contrast to the con stitutive expression of 3.5 kb mRNA, the expression of 2.6 kb mRNA inc reased markedly in accordance with those stages of brain development a t which we had previously demonstrated an increased immunoreactivity f or PDGF-B/c-SIS in neurons (Sasahara ef al., 1992). By PCR cloning and the RNase protection assay, we determined the complete sequence of ra t PDGF-B/c-sis, and found that the 2.6 kb transcript was a form of the 3.5 kb message truncated at the 5' end, and that the predominant 2.6 kb mRNA commenced 15 nt upstream of the signal peptide, Accordingly, i t is suggested that the truncation of 5' UTS contributes to the expres sion of PDGF-B/c-SIS protein in the CNS, Lack of translational inhibit ory 5' UTS of PDGF-B/c-sis transcript and resultant efficient protein translation have been reported in only a few transformed cells and cul tured umbilical vein endothelial cells, We have extended this knowledg e to the developing rat brain, and suggest that a similar mechanism co uld operate widely in non-transformed tissue in vivo.