Evidence map›Paper›PMID 31045216›Full record

ArticleNucleic acids research2019

Nonsense mutation-dependent reinitiation of translation in mammalian cells.

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

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Sarit CohenDepartment of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Lior KramarskiDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Shahar LeviDepartment of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Noa DesheDepartment of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Oshrit Ben DavidDepartment of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Eyal ArbelyDepartment of Chemistry and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Ben-Gurion University of the Negev · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 Δ40, Δ133 and Δ160p53. Here, we report that expression of all known N-truncated p53 isoforms by reinitiation is mechanistically feasible, including expression of the previously unidentified variant Δ66p53. 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.

Indexed as

Codon, NonsensePeptide Chain Initiation, TranslationalCell LineHEK293 CellsHumansNonsense Mediated mRNA DecayPromoter Regions, GeneticRNA, MessengerRNA StabilitySequence DeletionTumor Suppressor Protein p53Codon, NonsenseRNA, MessengerTumor Suppressor Protein p53

Identifiers

PMID31045216
PMCPMC6614817
OpenAlexW2943390208

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.