Identification of 3'UTR region implicated in tau mRNA stabilization in neuronal cells.
Tau, a neuronal microtubule-associated protein (MAP) plays an important role in the formation and maintenance of neuronal polarity. Tau mRNA is a stable message and exhibits a relatively long half-life in neuronal cells. The regulation of mRNA stability is a crucial determinant in controlling mRNA steady-state levels in neuronal cells and thereby influences gene expression. The half-lives of specific mRNAs may be dependent on specific sequences located at their 3'untranslated region (UTR), which in turn, may be recognized by tissue-specific proteins. To identify the sequence elements involved in tau mRNA stabilization, selected regions of the 3'UTR were subcloned downstream to c-fos reporter mRNA or to the coding region of the tau mRNA. Using stably transfected neuronal cells, we have demonstrated that a fragment of 240 bp (H fragment) located in the 3'UTR can stabilize c-fos and tau mRNAs. Analysis of stably transfected cells indicated that the transfected tau mRNAs are associated with the microtubules of neuronal cells, suggesting that this association may play a role in tau mRNA stabilization. This step may be a prerequisite in the multistep process leading to the subcellular localization of tau mRNA in neuronal cells.
Aronov
S
S
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Marx
R
R
Ginzburg
I
I
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002458:Cell Fractionation; D003078:Colchicine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D017930:Genes, Reporter; D006801:Humans; D008870:Microtubules / Q000502:physiology; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016716:PC12 Cells; D010957:Plasmids; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D012260:Ribonucleases; D014162:Transfection; D016875:tau Proteins / Q000235:genetics*
D020413:3' Untranslated Regions; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016875:tau Proteins; D012260:Ribonucleases; D003078:Colchicine