Regulated protein biosynthesis: lessons learned from tubulin

Ivana Gasic

Tubulins are abundant, highly conserved proteins that form the microtubule cytoskeleton, essential for cell organization, movement, and division. Maintaining tubulin quantity and quality is critical, as imbalances can disrupt microtubules and cause diseases like cancer and neurodevelopmental disorders. Tubulin autoregulation helps preserve homeostasis by triggering cotranslational degradation of tubulin mRNAs when tubulin protein levels are excessive. We have defined key molecular components of this pathway: TTC5, which senses nascent tubulin chains; SCAPER, an adaptor; and the CCR4-NOT complex, which drives mRNA decay. Our recent work shows that tubulin itself regulates TTC5 by sequestration—under steady-state conditions, TTC5 is inhibited, but when tubulin accumulates, TTC5 is released to induce mRNA degradation. Disrupting this regulation lowers tubulin mRNA levels and impairs mitosis. These findings clarify how tubulin biosynthesis is controlled and highlight the broader role of cotranslational mechanisms in adjusting protein production to cellular needs.