Figure 7. Model: Nonoptimal codons repress gene expression by two post-transcriptional mechanisms.

Nonoptimal codons slow translation elongation and can lead to a ribosome state with empty A and E sites. CNOT3 can sense this state and thus recruits the CCR4-NOT deadenylase complex to trigger mRNA destabilization. Slow elongation also reduces eIF4E and eIF4G1 binding, thereby repressing translation initiation. It is unclear what ribosome state is sensed—and how this information is transmitted—to suppress translation. Nevertheless, neither mRNA deadenylation nor decay is required for translational repression, and in fact, they seem to limit the extent to which translation is repressed.