Unpolymerized tubulin modulates the level of tubulin mRNAs

Although numerous studies have suggested ways in which the assembly of cytoskeletal proteins can be regulated physiologically, less information has been generated on the regulation of the synthesis of these proteins. Ben-Ze'ev et al. recently suggested that the synthesis of tubulin in mouse 3T6 cells is affected by the state of assembly of microtubules. We have investigated the level at which this apparent modulation of tubulin synthesis takes place, using cloned cDNA probes for alpha- and beta-tubulin mRNAs to measure the amounts of tubulin mRNAs combined with immunoprecipitation of tubulin to monitor the rate of protein synthesis. We have found that in many, but not all, cell types tubulin synthesis decreases very rapidly in response to microtubule inhibitors that increase the monomer pool. This decline in synthesis is associated with decline in the amounts of both alpha- and beta-tubulin mRNAs. Kinetic studies of tubulin protein synthesis and RNA levels suggest that the tubulin monomer may regulate the rate of tubulin mRNA transcription. It is likely that tubulin synthesis can be shut off quickly in the cell as the result of short half-lives of the tubulin mRNAs, which may be as short as 1--2 hr. These data suggest that the cell exploits the instability of the tubulin mRNAs as a means to regulate precise levels of the monomer-tubulin pool.