Nonsense mutation-dependent reinitiation of translation in mammalian cells

Sarit Cohen, Lior Kramarski, Shahar Levi, Noa Deshe, Oshrit Ben David, Eyal Arbely

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


In-frame stop codons mark the termination of translation. However, post-termination ribosomes can reinitiate translation at downstream AUG codons. In mammals, reinitiation is most efficient when the termination codon is positioned close to the 5'-proximal initiation site and around 78 bases upstream of the reinitiation site. The phenomenon was studied mainly in the context of open reading frames (ORFs) found within the 5'-untranslated region, or polycicstronic viral mRNA. We hypothesized that reinitiation of translation following nonsense mutations within the main ORF of p53 can promote the expression of N-truncated p53 isoforms such as ∆40, ∆133 and ∆160p53. Here, we report that expression of all known N-truncated p53 isoforms by reinitiation is mechanistically feasible, including expression of the previously unidentified variant ∆66p53. Moreover, we found that significant reinitiation of translation can be promoted by nonsense mutations located even 126 codons downstream of the 5'-proximal initiation site, and observed when the reinitiation site is positioned between 6 and 243 bases downstream of the nonsense mutation. We also demonstrate that reinitiation can stabilise p53 mRNA transcripts with a premature termination codon, by allowing such transcripts to evade the nonsense mediated decay pathway. Our data suggest that the expression of N-truncated proteins from alleles carrying a premature termination codon is more prevalent than previously thought.

Original languageEnglish
Pages (from-to)6330-6338
Number of pages9
JournalNucleic Acids Research
Issue number12
StatePublished - 9 Jul 2019

ASJC Scopus subject areas

  • Genetics


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