Autoregulation of actin synthesis requires the 3 '-UTR of actin mRNA and protects cells from actin overproduction

Monomeric (G) actin was shown to be involved in inhibiting its own synthesi s by an autoregulatory mechanism that includes enhanced degradation of the actin mRNA [Bershadsky et at., 1995; Lyubimova et al., 1997]. We show that the 3'-untranslated region (3'-UTR) of beta-actin mRNA, but not its 5'-untr anslated region, is important for this regulation. The level of full-length beta-actin mRNA in cells was reduced when actin filaments were depolymeriz ed by treatment with latrunculin A and elevated when actin polymerization w as induced by jasplakinolide. By contrast, the level of actin mRNA lacking the 3'-UTR remained unchanged when these drugs modulated the dynamics of ac tin assembly in the cell. Moreover, the transfection of cells with a constr uct encoding the autoregulation-deficient form of beta-actin mRNA led to ve ry high levels of actin expression compared with transfection with the cont rol actin construct and was accompanied by characteristic changes in cell m orphology and the structure of the actin cytoskeleton. These results sugges t that the autoregulatory mechanism working via the 3'-UTR of actin mRNA is involved in controlling the maintenance of a defined pool of actin monomer s that could be necessary for the proper organization of the microfilament system and the cytoskeleton-mediated signaling. J. Cell. Biochem. 76:1-12, 1999. (C) 1999 Wiley-Liss, Inc.