Fig. 2. Factors involved in mRNA surveillance. (A) During translation of a normal mRNA, the EJCs are displaced from the transcript by the translocating ribosome. Absence of a downstream EJC during translation termination results in a stable message. Translation release factors are shown in blue. (B) During translation termination of a PTC-containing transcript, the downstream EJC signals to the terminating ribosome via Upf3. Upf3, together with Upfs 1 and 2, may signal the presence of the PTC to the 5' end of the transcript, resulting in decapping and rapid exonucleolytic digestion of the mRNA. This model is based on yeast studies, and it is not yet known whether mammalian NMD also occurs by 5'3' exonucleolytic decay. (C) The ribosome translates through the poly-A tail in the absence of an in-frame termination codon. Ski7 is thought to bind to the empty ribosomal A site and recruit the exosome, resulting in rapid decay from the 3' end.