Vasopressin mRNA localization in nerve cells: Characterization of cis-acting elements and trans-acting factors

mRNA localization is a complex pathway. Besides mRNA sorting per se, this p rocess includes aspects of regulated translation. It requires protein facto rs that interact with defined sequences (or sequence motifs) of the transcr ipt, and the protein/RNA complexes are finally guided along the cytoskeleto n to their ultimate destinations. The mRNA encoding the vasopressin (VP) pr ecursor protein is localized to the nerve cell processes in vivo and in pri mary cultured nerve cells. Sorting of VP transcripts to dendrites is mediat ed by the last 395 nucleotides of the mRNA, the dendritic localizer sequenc e, and it depends on intact microtubules. In vitro interaction studies with cytosolic extracts demonstrated specific binding of a protein, enriched in nerve cell tissues, to the radiolabeled dendritic localizer sequence probe . Biochemical purification revealed that this protein is the multifunctiona l poly(A)-binding protein (PABP). It is well known for its ability to bind with high affinity to poly(A) tails of mRNAs, prerequisite for mRNA stabili zation and stimulation of translational initiation, respectively. With lowe r affinities, PABP can also associate with non-poly(A) sequences. The physi ological consequences of these PABP/RNA interactions are far from clear but may include functions such as translational silencing. Presumably, the tra nslational state of mRNAs subject to dendritic sorting is influenced by ext ernal stimuli. PABP thus could be a component required to regulate local sy nthesis of the VP precursor and possibly of other proteins.