Abstract
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.
Highlights
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
C-fos 3Ј-untranslated regions (3Ј-UTRs) Localizes a Reporter mRNA Sequence to Cytoskeletal-bound Polysomes and the Perinuclear Cytoplasm—To study the localization functions of the fos 3Ј-UTR, stable transfected cell lines were made that express chimeric gene constructs in which the fos 3Ј-UTR, fos⌬ 3Ј-UTR, or globin 3Ј-UTR were linked to the -globin coding region as a reporter
The data show that the c-fos 3Ј-UTR is sufficient to target a chimeric reporter to cytoskeletal-bound polysomes and the perinuclear cytoplasm
Summary
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. 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. The perinuclear localization of c-myc mRNA and its association with the cytoskeleton has been suggested to provide local synthesis of the protein that promotes efficient import of the newly synthesized protein into the nucleus This could be important in the case of unstable transcription factors; it is not clear if mRNAs coding for other transcription factors are localized by a similar mechanism. Using chimeric -globinfos 3Ј-UTR gene constructs in fibroblast cell lines, reporter stability was found to increase severalfold when the translation of the reporter was decreased [17, 18] This indicated some link between translation and ARE-dependent mRNA degradation of the c-fos mRNA; the mechanisms require further clarification. It is not known if the c-fos mRNA is localized or if this association with the cytoskeleton involves a signal within the 3Ј-UTR
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