CIS-ACTING SIGNALS AND TRANS-ACTING PROTEINS ARE INVOLVED IN TAU MESSENGER-RNA TARGETING INTO NEURITES OF DIFFERENTIATING NEURONAL CELLS

Tau microtubule-associated protein is a neuron specific protein found primarily in axons and is developmentally regulated, The function of t au is in stabilization of microtubules, which is important in establis hing and maintaining neuronal morphology. Axonal localization of tau i nvolves a multistep process which is studied in differentiating primar y neuronal culture. The initial step involves sorting and subcellular localization of its encoding mRNA into the proximal portion of the axo n. Using the transfection assay into neuronal cells, we have demonstra ted that sequences located in the 3'-untranslated region include a cis -acting signal which is involved in tau mRNA targeting. In addition, u sing ultraviolet cross-linking assay, two RNA-binding proteins of 43 a nd 38 kDa were identified, that exhibit specific binding to a minimal sequence of 91 nucleotides located within the same functional region, which is involved in targeting. The 43 and 38-kDa RNA-binding proteins are present in cytoplasmic extracts, prepared from neuronal cells, an d in isolated microtubule preparations, Our results support a novel mo del in which cis-acting signals, together with RNA-binding proteins, a re involved in the targeting of tau mRNA, that may ultimately lead to its axonal localization.