Tubulin autoregulation controls the biosynthesis of γ-tubulin to ensure mitotic fidelity

Microtubule organization relies on the precise control of tubulin abundance to ensure accurate cytoskeletal function and faithful cell division. While - and {beta}-tubulin levels are controlled by a well-characterized autoregulatory pathway that triggers co-translational mRNA decay in response to excess soluble tubulin, how cells regulate the abundance of the core microtubule nucleator {gamma}-tubulin has remained unclear. Here, we show that {gamma}-tubulin is regulated by the canonical tubulin autoregulatory machinery. We find that {gamma}-tubulin-encoding mRNAs are downregulated in response to elevated soluble {beta}-tubulin levels. This regulation requires TTC5 to co-translationally recognize a conserved amino-terminal MPREI motif in nascent {gamma}-tubulin proteins, and further recruit SCAPER and CCR4-NOT complex, targeting {gamma}-tubulin mRNAs for decay. Disruption of this regulatory mechanism elevates {gamma}-tubulin protein levels, increases centrosomal microtubule nucleation output, and compromises mitotic fidelity. Together, our findings establish {gamma}-tubulin as a previously unrecognized substrate of tubulin autoregulation and reveal coordinated control of tubulin biosynthesis as a key mechanism for tuning microtubule nucleation and ensuring accurate chromosome segregation.