Translational repression of NMD targets by GIGYF2 and EIF4E2

PLoS Genet. 2021 Oct 19;17(10):e1009813. doi: 10.1371/journal.pgen.1009813. eCollection 2021 Oct.


Translation of messenger RNAs (mRNAs) with premature termination codons produces truncated proteins with potentially deleterious effects. This is prevented by nonsense-mediated mRNA decay (NMD) of these mRNAs. NMD is triggered by ribosomes terminating upstream of a splice site marked by an exon-junction complex (EJC), but also acts on many mRNAs lacking a splice junction after their termination codon. We developed a genome-wide CRISPR flow cytometry screen to identify regulators of mRNAs with premature termination codons in K562 cells. This screen recovered essentially all core NMD factors and suggested a role for EJC factors in degradation of PTCs without downstream splicing. Among the strongest hits were the translational repressors GIGYF2 and EIF4E2. GIGYF2 and EIF4E2 mediate translational repression but not mRNA decay of a subset of NMD targets and interact with NMD factors genetically and physically. Our results suggest a model wherein recognition of a stop codon as premature can lead to its translational repression through GIGYF2 and EIF4E2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carrier Proteins / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Codon, Nonsense / genetics
  • Codon, Terminator / genetics
  • Eukaryotic Initiation Factor-4E / genetics*
  • Exons / genetics
  • HEK293 Cells
  • Humans
  • K562 Cells
  • Nonsense Mediated mRNA Decay / genetics*
  • Protein Biosynthesis / genetics*
  • RNA Splicing / genetics
  • RNA, Messenger / genetics*


  • 3' Untranslated Regions
  • Carrier Proteins
  • Codon, Nonsense
  • Codon, Terminator
  • EIF4E2 protein, human
  • Eukaryotic Initiation Factor-4E
  • GIGYF2 protein, human
  • RNA, Messenger