The dark proteome: translation from noncanonical open reading frames

Bradley W. Wright, Zixin Yi, Jonathan S. Weissman, Jin Chen

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations


Omics-based technologies have revolutionized our understanding of the coding potential of the genome. In particular, these studies revealed widespread unannotated open reading frames (ORFs) throughout genomes and that these regions have the potential to encode novel functional (micro-)proteins and/or hold regulatory roles. However, despite their genomic prevalence, relatively few of these noncanonical ORFs have been functionally characterized, likely in part due to their under-recognition by the broader scientific community. The few that have been investigated in detail have demonstrated their essentiality in critical and divergent biological processes. As such, here we aim to discuss recent advances in understanding the diversity of noncanonical ORFs and their roles, as well as detail biologically important examples within the context of the mammalian genome.

Original languageEnglish (US)
Pages (from-to)243-258
Number of pages16
JournalTrends in Cell Biology
Issue number3
StatePublished - Mar 2022


  • microproteins
  • noncanonical ORFs
  • ribosome profiling
  • short ORFs
  • translation

ASJC Scopus subject areas

  • Cell Biology


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