Fig. 4.

Gcn1 as a checkpoint for disome collision. (A) Amino acid starvation leads to increased binding of uncharged tRNAs within the ribosomal A-site, leading to translation slowdown/stalling and collisions. (B) Colliding ribosomes (disomes) are recognized by Gcn1-Gcn20. (C) Gcn1 in turn recruits Gcn2 via direct interaction with the Gcn2 N-terminal RWD domain. Activation of Gcn2 results in the phosphorylation of eIF2α and induction of the GAAC pathway. (D) Translating ribosomes may also encounter specific mRNA sequences/structures and/or nascent polypeptide motifs that induce a translational slow-down or pausing, also leading to collisions and disome formation, which are known as substrates for the ribosome quality control but are also recognized by Gcn1. (E) Concomitant recruitment of the Rbg2-Gir2 to the leading ribosome by Gcn1 allows Rbg2 to resolve the slowdown, while Gir2 prevents the recruitment and activation of Gcn2 and eventually allows translation to resume (F).