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 synthesis by an autoregulatory mechanism that includes enhanced degradation of the actin mRNA [Bershadsky et al., 1995; Lyubimova et al., 1997]. We show that the 3'-untranslated region (3'-UTR) of beta-actin mRNA, but not its 5'-untranslated region, is important for this regulation. The level of full-length beta-actin mRNA in cells was reduced when actin filaments were depolymerized by treatment with latrunculin A and elevated when actin polymerization was induced by jasplakinolide. By contrast, the level of actin mRNA lacking the 3'-UTR remained unchanged when these drugs modulated the dynamics of actin assembly in the cell. Moreover, the transfection of cells with a construct encoding the autoregulation-deficient form of beta-actin mRNA led to very high levels of actin expression compared with transfection with the control actin construct and was accompanied by characteristic changes in cell morphology and the structure of the actin cytoskeleton. These results suggest that the autoregulatory mechanism working via the 3'-UTR of actin mRNA is involved in controlling the maintenance of a defined pool of actin monomers that could be necessary for the proper organization of the microfilament system and the cytoskeleton-mediated signaling.
Lyubimova
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Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Bershadsky
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AD
Ben-Ze'ev
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D020413:3' Untranslated Regions; D016475:3T3 Cells; D000199:Actins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002460:Cell Line; D017931:DNA Primers; D047630:Depsipeptides; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D017384:Sequence Deletion; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D020413:3' Untranslated Regions; D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017931:DNA Primers; D047630:Depsipeptides; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D013844:Thiazoles; D053778:Thiazolidines; C057531:jasplakinolide; C037067:latrunculin A