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

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, Ca 2+ ‐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.