Translational surveillance pathways under consideration. (A) Translation of a normal mRNA. Ribosomes (gray) load near the trimethylguanosine cap (m2,2,7G) and locate a start codon (green stoplight). Ribosomes elongate until they terminate at a stop codon (red octagon). Upon termination, protein is released, and ribosomes are recycled for further rounds of translation. (B) Nonsense-mediated mRNA decay (NMD) arises from translation termination at a premature stop codon. The mRNA is destabilized through the action of at least seven SMG proteins. (C) Nonstop Decay arises from translation to the 3′ end of an mRNA, which can arise from mRNA cleavage (left) or polyadenylation upstream of a stop codon (right). The mRNA and nascent protein are degraded, and the ribosome is rescued. (D) No-Go Decay arises when a ribosome stalls as a result of a roadblock during elongation (yellow triangle). Such roadblocks include RNA hairpins, rare codons, and polybasic (Arg or Lys) amino acid runs. As with Nonstop Decay, the mRNA and nascent protein are degraded, and the ribosome is rescued.