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J. Biol. Chem., Vol. 276, Issue 17, 13593-13599, April 27, 2001
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From the 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
mRNA Localization by a 145-Nucleotide Region of the
c-fos 3'- Untranslated Region
LINKS TO TRANSLATION BUT NOT STABILITY*
,¶
Rowett Research Institute, Bucksburn,
Aberdeen, AB21 9SB Scotland, United Kingdom, § Institut
de Genetique Moleculaire, CNRS UMR 5535, 1919 Route de Mende, 34293 Montpellier cedex 5, France, and the ¶ Department of
Biological and Nutritional Sciences, University of Newcastle, Kings
Road, Newcastle-upon-Tyne, NE1 7RU, England, United Kingdom
-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 -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.
*
This work was supported by the Scottish Office Agriculture,
Environment, and Fisheries Department and by Grant BioMed BHM4 CT95-0995 from the European Community.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
44-191-222-8744; Fax: 44-191-222-8684; E-mail:
j.e.hesketh@ncl.ac.uk.
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