DIFFERENTIAL SUBCELLULAR MESSENGER-RNA TARGETING - DELETION OF A SINGLE NUCLEOTIDE PREVENTS THE TRANSPORT TO AXONS BUT NOT TO DENDRITES OF RAT HYPOTHALAMIC MAGNOCELLULAR NEURONS

It has previously been shown that mRNA encoding the arginine vasopress in (AVP) precursor is targeted to axons of rat magnocellular neurons o f the hypothalamo-neurohypophyseal tract. In the homozygous Brattlebor o rat, which has a G nucleotide deletion in the coding region of the A VP gene, no such targeting is observed although the gene is transcribe d. RNase protection and heteroduplex analyses demonstrate that, in het erozygous animals, which express both alleles of the AVP gene, the wil d-type but not the mutant transcript is subject to axonal compartmenta tion. In contrast, wild-type and mutant AVP mRNAs are present in dendr ites, These data suggest the existence of different mechanisms for mRN A targeting to the two subcellular compartments. Axonal mRNA localizat ion appears to take place after protein synthesis; the mutant transcri pt is not available for axonal targeting because it lacks a stop codon preventing its release from ribosomes. Dendritic compartmentation, on the other hand, is likely to precede translation and, thus, would be unable to discriminate between the two mRNAs.