Identification of 3 ' UTR region implicated in tau mRNA stabilization in neuronal cells

Tau, a neuronal microtuble-associated protein (MAP) plays an important role in the formation and maintenance of neuronal polarity. Tau mRNA is a stabl e message and exhibits a relatively long half-life in neuronal cells. The r egulation of mRNA stability is a crucial determinant in controlling mRNA st eady-state levels in neuronal cells and thereby influences gene expression. The half-lives of specific mRNAs may be dependent on specific sequences lo cated at their 3'untranslated region (UTR), which in turn, may be recognize d by tissue-specific proteins. To identify the sequence elements involved in tau mRNA stabilization, selec ted regions of the 3'UTR were subcloned downstream to c-fos reporter mRNA o r to the coding region of the tau mRNA. Using stably transfected neuronal c ells, we have demonstrated that a fragment of 240 bp (H fragment) located i n the 3'UTR can stabilize c-Jos and tau mRNAs. Analysis of stably transfect ed cells indicated that the transfected tau mRNAs are associated with the m icrotubules of neuronal cells, suggesting that this association may play a role in tau mRNA stabilization. This step may be a prerequisite in the mult istep process leading to the subcellular localization of tau mRNA in neuron al cells.