ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation

ELAV proteins are implicated in regulating the stability and translation of cytokine and growth regulatory mRNAs such as GM-CSF, IL-2, c-myc, c-fos an d GLUT1 by binding to their AU-rich 3'UTRs, The tissue-specific ELAV protei n HuB (aka, Hel-N1) is predominantly cytoplasmic and has been shown to stab ilize GLUT1 and c-myc mRNAs and to increase their translation following ect opic expression in 3T3-L1 cells. We report that the most widely expressed m ouse ELAV protein, mHuA, is predominately nuclear in cultured NIH-3T3 cells , but is localized in the cytoplasm during early G(1) of the cell cycle. Th erefore, much like the primarily cytoplasmic HuB, HuA becomes temporally lo calized in the cytoplasm where it can potentially regulate the stability or translation of bound mRNAs, Moreover, we report that stimulation of mouse spleen cells using either mitogenic or sub-mitogenic levels of anti-CD3/CD2 8 resulted in a dramatic increase in the level of HuA, Upregulation of HuA corresponds to previously documented increases in cytokine expression which are due to increased mRNA stability following T cell activation. Consisten t with these findings, HuA was down regulated in quiescent cells and upregu lated in 3T3 cells following serum stimulation. The increase of murine HuA during the cell cycle closely resembles that of cyclin B1 which peaks in G( 2)/M. Together with our earlier studies, these data indicate that mammalian ELAV proteins function during cell growth and differentiation due in part to their effects on posttranscriptional stability and translation of multip le growth regulatory mRNAs, This supports the hypothesis that ELAV proteins can function as transacting factors which affect a default pathway of mRNA degradation involved in the expression of growth regulatory proteins.