Selective tubulin mRNA degradation is triggered when cells sense excess free tubulin levels, e.g., due to microtubule (MT) depolymerization, as depicted in the bottom schematic (N: nucleus). Under these conditions, TTC5 is liberated from an elusive inhibitory factor17(not shown). This allows TTC5 to selectively bind tubulin-translating ribosomes by interacting with the conserved N-terminal peptide motif (Met-Arg-Glu-Ile or MREI, shown in dark blue) and a surface around the ribosomal exit tunnel. SCAPER recruitment is, in turn, facilitated by a composite interaction surface formed by TTC5 and the ribosome. The CCR4-NOT complex uses its CNOT11 subunit to bind an extended -helical domain of SCAPER and its nuclease subunit(s) to deadenylate tubulin mRNA to initiate its subsequent degradation.
