14‐3‐3σ is a p37 AUF1‐binding protein that facilitates AUF1 transport and AU‐rich mRNA decay

Short‐lived cytokine mRNAs contain an AU‐rich destabilizing element (ARE). AUF1 proteins bind the ARE, undergo shuttling, and promote cytoplasmic ARE‐mRNA decay through a poorly understood mechanism. We therefore identified AUF1‐interacting proteins that may play a role in ARE‐mRNA decay. We used mass‐spectrometry to identify 14‐3‐3σ protein as an AUF1‐interacting protein. 14‐3‐3σ binds selectively and strongly to p37 AUF1 and to a lesser extent to the p40 isoform, the two isoforms most strongly associated with ARE‐mRNA decay, but not to the two larger isoforms, p42 and p45. The 14‐3‐3σ interaction site on p37 was mapped to a region found only in the two smaller AUF1 isoforms and which overlaps a putative nuclear localization signal (NLS). Stable overexpression of 14‐3‐3σ significantly increased cytoplasmic accumulation of p37 AUF1 and reduced the steady‐state level and half‐life of a reporter ARE‐mRNA. siRNA silencing of AUF1 eliminated the effect of 14‐3‐3σ overexpression. 14‐3‐3σ therefore binds to p37 AUF1, retains it in the cytoplasm probably by masking its NLS, and enhances rapid turnover of ARE‐mRNAs.