mRNA localization by a 145-nucleotide region of the c-fos 3′-untranslated region -: Links to translation but not stability

The presence of a localization signal in the 3'-untranslated region of c-fos mRNA was investigated by in situ hybridization and cell fractionation techniques. Cells were transfected with chimeric gene constructs in which the beta -globin coding region was used as a reporter and linked to either its own 3'-untranslated region, the c-fos 3'-untranslated region, or the c-fos 3'-untranslated region containing different deletions. Replacement of the endogenous beta -globin 3'-untranslated region by that from c-fos caused a redistribution of the transcripts so that they were recovered in cytoskeletal-bound polysomes and seen localized in the perinuclear cytoplasm, Deletion of the AU-rich instability region did not affect transcript localization, but removal of a distinct 145-nucleotide region of the 3'-untranslated region abolished it. The prevention of transcript translation by desferrioxamine led to a marked loss of transcript localization, independent of mRNA instability. The data show that the 3'-untranslated region of c-fos mRNA, as c-myc, contains a localization signal, which targets the mRNA to the perinuclear cytoskeleton. We propose that this is important to ensure efficient nuclear import of these key regulatory proteins. mRNA localization by the fos 3'-untranslated region is independent of mRNA instability, and the two are determined by different regulatory elements.