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Ribosome stalling on the poly(A) tail of non-stop mRNAs triggers a multi-faceted response. The mechanism of stalling (left) involves a combination of slowed elongation due to interactions of the poly-lysine peptide (encoded by AAA codons) with the negatively charged tunnel surface and unfavorable helical formation of the poly(A) sequence in the A-site that impairs decoding. Stalling of a ribosome on poly(A) leads to collision with a trailing ribosome (right). The compound surface of the collided disome serves as a platform to recruit collision-specific effectors that mediate a range of outcomes as indicated by the arrows: (1) cap-dependent translation initiation inhibition by GIGYF2 and 4EHP; (2) collision dissociation and ribosome-associated quality control (RQC) by ZNF598, ASCC, and other factors; (3) mRNA decay by the SKI complex, Cue2, and the exosome; and (4) stress signaling via the kinases ZAK and GCN2.

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