Pervasive functional translation of noncanonical human open reading frames

Ribosome profiling has revealed pervasive but largely uncharacterized translation outside of canonical coding sequences (CDSs). In this work, we exploit a systematic CRISPR-based screening strategy to identify hundreds of noncanonical CDSs that are essential for cellular growth and whose disruption elicits specific, robust transcriptomic and phenotypic changes in human cells. Functional characterization of the encoded microproteins reveals distinct cellular localizations, specific protein binding partners, and hundreds of microproteins that are presented by the human leukocyte antigen system. We find multiple microproteins encoded in upstream open reading frames, which form stable complexes with the main,…

• HH
  Howard Hughes Medical Institute
• JC
  Jane Coffin Childs Memorial Fund for Medical Research
• IG
  Innovative Genomics Institute
• M
  Max-Planck-Gesellschaft
• NI
  National Institutes of Health

  Awards: K99/R00, GM134154, HG009490, RM1 HG009490
• DA
  Defense Advanced Research Projects Agency

  Award: HR0011-17-2-0043
• NO
  NIH Office of the Director

  Award: HG009490
• DS
  Defense Sciences Office, DARPA

  Award: HR0011-17-2-0043