The CCR4-NOT deadenylase complex mediates tubulin autoregulation via specific adapters CNOT10 and CNOT11.

Tubulin autoregulation maintains cellular microtubule homeostasis by triggering rapid degradation of tubulin mRNAs in response to an increase in soluble α- and β-tubulin levels. Through siRNA knock-down of several RNA decay pathways coupled with Roadblock-qPCR kinetic measurements, we independently validate and extend prior work by identifying the CCR4-NOT deadenylase complex components CNOT1, CNOT10, and CNOT11 as central effectors both in tubulin autoregulation and basal tubulin mRNA stability. In contrast, depletion of ribosome quality control and other decay factors has little effect. These findings corroborate CCR4-NOT adaptors as essential effectors of tubulin autoregulation and provide molecular entry points to dissect microtubule homeostasis.