Lack of evidence for ribosomal frameshifting in ATP7B mRNA decoding

Mol Cell. 2022 Oct 6;82(19):3745-3749.e2. doi: 10.1016/j.molcel.2022.08.024. Epub 2022 Sep 16.


The research article describing the discovery of ribosomal frameshifting in the bacterial CopA gene also reported the occurrence of frameshifting in the expression of the human ortholog ATP7B based on assays using dual luciferase reporters. An examination of the publicly available ribosome profiling data and the phylogenetic 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 using 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 reporter 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.

Keywords: ATP7B; artifacts; dual reporters; mRNA decoding; ribosomal frameshifting; ribosome profiling; translation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Copper-Transporting ATPases / metabolism*
  • Frameshifting, Ribosomal* / genetics
  • Humans
  • Luciferases / genetics
  • Nucleic Acid Conformation
  • Phylogeny
  • Polyproteins* / genetics
  • Polyproteins* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Polyproteins
  • RNA, Messenger
  • Luciferases
  • ATP7B protein, human
  • Copper-Transporting ATPases