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Annexin A2 binds to the localization signal in the 3′ untranslated region of c-myc mRNA

Lookup NU author(s): Professor Zofia Chrzanowska-Lightowlers, Professor John Hesketh

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Abstract

Messenger RNA trafficking, which provides a mechanism for local protein synthesis, is dependent on cis-acting sequences in the 3′ untranslated regions (3′UTRs) of the mRNAs concerned acting together with trans-acting proteins. The C-MYC transcription factor is a proto-oncogene product involved in cell proliferation, differentiation and apoptosis. Localization of c-myc mRNA to the perinuclear cytoplasm and its association with the cytoskeleton is determined by a signal in the 3′UTR. Here we show the specific binding of a trans-acting factor to the perinuclear localization element in the 3′UTR of c-myc mRNA and identify this protein as annexin A2. Gel retardation and UV cross-linking experiments showed that proteins in fibroblast extracts formed complexes with the region of c-myc 3′UTR implicated in localization; a protein of ≈36 kDa exhibited specific, Ca2+-dependent binding. Binding was reduced by introduction of a mutation that abrogates localization. Using RNA-affinity columns followed by gel electrophoresis and mass spectrometry this protein was identified as annexin A2. The RNA-protein complex formed by cell extracts was further retarded by anti-(annexin A2). Purified annexin A2 bound to the same region of the c-myc 3′UTR but binding was reduced by introduction of a mutation, as with cell extracts. It is proposed that binding of annexin A2 to the localization signal in the c-myc mRNA leads to association with the cytoskeleton and perinuclear localization. The data indicate a novel functional role for the RNA-binding properties of annexin A2 in perinuclear localization of mRNA and the association with the cytoskeleton.


Publication metadata

Author(s): Mickleburgh I, Burtle B, Hollas H, Campbell G, Chrzanowska-Lightowlers Z, Vedeler A, Hesketh J

Publication type: Article

Publication status: Published

Journal: FEBS Journal

Year: 2005

Volume: 272

Issue: 2

Pages: 413-421

Print publication date: 01/01/2005

ISSN (print): 1742-464X

ISSN (electronic): 1742-4658

Publisher: Wiley

URL: http://dx.doi.org/10.1111/j.1742-4658.2004.04481.x

DOI: 10.1111/j.1742-4658.2004.04481.x

PubMed id: 15654879


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