Annexin A2 is a novel RNA-binding protein

Annexin A2 (ANXA2) is a Ca2+-binding protein that is up-regulated in virally transformed cell lines and in human tumors. Here, we show that ANXA2 binds directly to both ribonucleotide homopolymers and human c-myc RNA. ANXA2 was shown to bind specifically to poly( G) with high affinity (K-d = 60 nM) and not to poly( A), poly( C), or poly( U). The binding of ANXA2 to poly( G) required Ca2+ (A(50%) = 10 muM). The presence of RNA in the immunoprecipitates of ANXA2 isolated from HeLa cells established that ANXA2 formed a ribonucleoprotein complex in vivo. Sucrose gradient analysis showed that ANXA2 associates with ribonucleoprotein complexes and not with polyribosomes. Reverse transcriptase-PCR identified c-myc mRNA as a component of the ribonucleoprotein complex formed by ANXA2 in vivo, and binding studies confirmed a direct interaction between ANXA2 and c-myc mRNA. Transfection of LNCaP cells with the ANXA2 gene resulted in the up-regulation of c-Myc protein. These findings identify ANXA2 as a Ca2+-dependent RNA-binding protein that interacts with the mRNA of the nuclear oncogene, c-myc.