INTERACTION OF AU-RICH SEQUENCE BINDING-PROTEINS WITH ACTIN - POSSIBLE INVOLVEMENT OF THE ACTIN CYTOSKELETON IN LYMPHOKINE MESSENGER-RNA TURNOVER

In the current study, we report that cytochalasin-induced disruption o f microfilaments stabilizes lymphokine mRNAs in activated human periph eral blood lymphocytes. Parallel with this, a dose-and time-dependent increase in AU-rich sequence binding protein (AUPB) activities is appa rent in the nonionic detergent-resistant fractions of these cells, sug gesting that cytochalasin-induced modulation of lymphokine mRNA stabil ity might be mediated through cytoplasmic AUBPs. We provide evidence t hat some of the AUBPs can be immunoprecipitated with anti-actin antibo dies, implicating the potential of these proteins to associate with th e actin-based cytoskeleton in vivo. Moreover, disruption of the microf ilament network by cytochalasins produces increased immunoprecipitable actin-AUBP complexes in the detergent-resistant cytoplasmic subfracti ons of lymphocytes. We show that cytochalasin-induced changes in AUBP activities are parallel with their higher binding affinity to RNA cont aining AU-rich instability sequence element as judged by in vitro comp etition and in vivo ultraviolet-crosslinking analysis. Correlation of these findings with changes in mRNA stability indicates that the actin cytoskeleton may play a physiologically important role in posttranscr iptional regulation of lymphokine gene expression during early lymphoc yte activation. (C) 1997 Wiley-Liss, Inc.