4.8 Article

Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

期刊

MOLECULAR CELL
卷 82, 期 19, 页码 3745-+

出版社

CELL PRESS
DOI: 10.1016/j.molcel.2022.08.024

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资金

  1. SFI-HRB-Wellcome Trust Biomed-ical Research Partnership Investigator Award in Science [210692/Z/18/]
  2. Irish Research Council Advanced Laureate [IRCLA/2019/74]
  3. Science Foundation Ireland (SFI Centre for Research Training in Genomics Data Science [18/CRT/6214]

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The research article discusses the discovery of ribosomal frameshifting in the bacterial CopA gene and its occurrence in the human ortholog ATP7B. However, further examination of the evidence raises doubts about the validity of this claim, as well as the interference of other factors in the experimental results.
The research article describing the discovery of ribosomal frameshifting in the bacterial CopA gene also re-ported the occurrence of frameshifting in the expression of the human ortholog ATP7B based on assays us-ing dual luciferase reporters. An examination of the publicly available ribosome profiling data and the phylo-genetic analysis of the proposed frameshifting site cast doubt on the validity of this claim and prompted us to reexamine the evidence. We observed similar apparent frameshifting efficiencies as the original authors us-ing the same type of vector that synthesizes both luciferases as a single polyprotein. However, we noticed anomalously low absolute luciferase activities from the N-terminal reporter that suggests interference of re-porter activity or levels by the ATP7B test cassette. When we tested the same proposed ATP7B frameshifting cassette in a more recently developed reporter system in which the reporters are released without being included in a polyprotein, no frameshifting was detected above background levels.

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