Figure 4.

Nonsense‐mediated mRNA decay and mechanisms of viral avoidance. (a) When the translation machinery reaches the stop codon of a normal mRNA, the eukaryotic release factors eRF1 and eRF3 are recruited to the ribosome, in part via interactions with PABP. This results in efficient translation termination and re‐initiation. (b) When mRNAs containing a premature stop codon (PTC) are translated, the presence of EJCs downstream of the PTC, coupled with inefficient interactions between PABP and the termination factors, triggers nonsense‐mediated decay (NMD). NMD is induced by recruitment of Upf1–3 and the Smg proteins; cleavage by the endonuclease Smg6 triggers degradation of the mRNA fragments. Viruses such as HIV‐1 regulate the alterative splicing of their genomic RNAs to avoid the presence of EJCs downstream of stop codons. (c) The unspliced RNA of Rous sarcoma virus has a very long 3^′ UTR, which is stabilized by the RSE element that directly inhibits NMD. This element may artificially ‘shorten’ the 3^′ UTR by making contacts with sequences close to the poly(A) tail.