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Lookup NU author(s): Professor John Hesketh
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In eukaryotic cells, several mRNAs including those of c-myc and c-fos are localized to the perinuclear cytoplasm and associated with the cytoskeleton. The localization element of c-myc mRNA is present within its 3′UTR (3′-untranslated region) but the precise nature of this signal has remained unidentified. Chemical/ enzymatic cleavage with RNases (ribonucleases) and lead have identified single-stranded and double-stranded regions in RNA transcripts of nucleotides 194-280 of the c-myc 3′UTR. Combined with computer predicted structure these results indicate that this region folds so that part of it forms a stem-loop structure. A mutation, that has been previously shown to prevent localization, leads to a different secondary RNA structure in this region as indicated by altered cleavage patterns. Competitive gel-retardation assays, using labelled transcripts corresponding to nucleotides 205-280 of c-myc 3′UTR, and fibroblast extracts revealed that the stem-loop region was sufficient for RNA-protein complex formation. In situ hybridization studies in cells transfected with reporter constructs, in which all or parts of the region corresponding to this stem-loop were linked to β-globin, indicated that this region was sufficient for localization and that deletion of the nucleotides corresponding to the proposed upper-stem or terminal loop prevented localization. Our hypothesis is that an AU-rich stem-loop structure within nt 222-267 in the c-myc 3′UTR forms the perinuclear localization signal. Bioinformatic analysis suggests that this signal shares features with 3′UTRs of other localized mRNAs and that these features may represent a conserved form of signal in mRNA localization mechanisms. © 2005 Biochemical Society.
Author(s): Chabanon H, Mickleburgh I, Burtle B, Pedder C, Hesketh J
Publication type: Article
Publication status: Published
Journal: Biochemical Journal
Year: 2005
Volume: 392
Issue: 3
Pages: 475-483
Print publication date: 15/12/2005
ISSN (print): 0264-6021
ISSN (electronic): 1470-8728
Publisher: Portland Press Ltd.
URL: .http:dx.doi.org/10.1042/BJ20050812
DOI: 10.1042/BJ20050812
PubMed id: 16042622
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