ROLE OF HIGHLY CONSERVED PYRIMIDINE-RICH SEQUENCES IN THE 3'-UNTRANSLATED REGION OF THE GAP-43 MESSENGER-RNA IN MESSENGER-RNA STABILITY ANDRNA-PROTEIN INTERACTIONS

We have shown previously that the mRNA for the growth-associated prote in GAP-43 is selectively stabilized during neuronal differentiation. I n this study, we explored the role of its highly conserved 3' untransl ated region (3'UTR) in mRNA stability and RNA-protein interactions. Th e 3'UTRs of the rat and chicken GAP-43 mRNAs show 78% sequence identit y, which is equivalent to the conservation of their coding regions. In rat PC12 cells stably transfected with the full-length rat or chicken GAP-43 cDNAs, the transgene mRNAs decayed with same half-life of abou t 3 h. The GAP-43 3'UTR also caused the rabbit beta-globin mRNA to dec ay with a half-life of 4 h, indicating that the major determinants for GAP-43 mRNA stability are localized in its highly conserved 3'UTR. Th ree brain cytosolic RNA-binding proteins (molecular mass 40, 65 and 95 kDa) were found to interact with both the rat and chicken GAP-43 mRNA s. These RNA-protein interactions were specific and involved pyrimidin e-rich sequences in the 3'UTR. Like the GAP-43 mRNA, the activity of t hese proteins was enriched in brain and increased during development. We propose that highly conserved pyrimidine-rich sequences in the 3'UT R of this mRNA regulate GAP-43 gene expression via interactions with s pecific RNA-binding proteins.