Interaction of AU-rich sequence binding proteins with actin: Possible involvement of the actin cytoskeleton in lymphokine mRNA turnover

Abstract

In the current study, we report that cytochalasin-induced disruption of microfilaments stabilizes lymphokine mRNAs in activated human peripheral blood lymphocytes. Parallel with this, a dose-and time-dependent increase in AU-rich sequence binding protein (AUPB) activities is apparent in the nonionic detergentresistant fractions of these cells, suggesting that cytochalasin-induced modulation of lymphokine mRNA stability might be mediated through cytoplasmic AUBPs. We provide evidence that some of the AUBPs can be immunoprecipitated with anti-actin antibodies, implicating the potential of these proteins to associate with the actin-based cytoskeleton in vivo. Moreover, disruption of the microfilament network by cytochalasins produces increased immunoprecipitable actin-AUBP complexes in the detergent-resistant cytoplasmic subfractions of lymphocytes. We show that cytochalasin-induced changes in AUBP activities are parallel with their higher binding affinity to RNA containing AU-rich instability sequence element as judged by in vitro competition 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 posttranscriptional regulation of lymphokine gene expression during early lymphocyte activation.

Mammalian Hsp70 and Hsp110 Proteins Bind to RNA Motifs Involved in mRNA Stability

“…This suggests that RNA binding by the N terminus of the chaperone molecule involves other, presumably larger regions within the ATP-binding domain than those responsible for the binding of ATP. This view is also consistent with our previous finding that actin, whose structure and folding topology are nearly identical to that of the ATPase fragment of Hsc70 (32), does not bind RNA (39).…”

Actin Cytoskeleton Organization and Posttranscriptional Regulation of Endothelial Nitric Oxide Synthase During Cell Growth

“…34,35 Cytochalasin-induced disruption of lymphocyte microfilaments resulted in more stable IL-2 and tumor necrosis factor-␣ mRNAs, and this was associated with an altered subcellular localization of destabilizing RNA-binding proteins. These proteins could be immunoprecipitated with anti-actin antibodies.…”

Cytoskeletal architecture differentially controls post-transcriptional processing of IL-6 and IL-8 mRNA in airway epithelial-like cells

“…A link between mRNA degradation and the cytoskeleton was described earlier for IL-2 mRNA. IL-2 mRNA degradation was reduced after disruption of the actin cytoskeleton by cytochalasin B in PBMCs [21].…”