Translation of small downstream ORFs enhances translation of canonical main open reading frames

EMBO J. 2020 Sep 1;39(17):e104763. doi: 10.15252/embj.2020104763. Epub 2020 Aug 3.


In addition to canonical open reading frames (ORFs), thousands of translated small ORFs (containing less than 100 codons) have been identified in untranslated mRNA regions (UTRs) across eukaryotes. Small ORFs in 5' UTRs (upstream (u)ORFs) often repress translation of the canonical ORF within the same mRNA. However, the function of translated small ORFs in the 3' UTRs (downstream (d)ORFs) is unknown. Contrary to uORFs, we find that translation of dORFs enhances translation of their corresponding canonical ORFs. This translation stimulatory effect of dORFs depends on the number of dORFs, but not the length or peptide they encode. We propose that dORFs represent a new, strong, and universal translation regulatory mechanism in vertebrates.

Keywords: dORF; ribosome profiling; translation efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Codon* / genetics
  • Codon* / metabolism
  • Open Reading Frames*
  • Protein Biosynthesis*
  • Zebrafish Proteins* / biosynthesis
  • Zebrafish Proteins* / genetics
  • Zebrafish* / genetics
  • Zebrafish* / metabolism


  • Codon
  • Zebrafish Proteins