The ASC-1 complex promotes translation initiation by scanning ribosomes

EMBO J. 2023 Jun 15;42(12):e112869. doi: 10.15252/embj.2022112869. Epub 2023 Apr 24.


Translation initiates when the eIF4F complex binds the 5' mRNA cap, followed by 5' untranslated region scanning for the start codon by scanning ribosomes. Here, we demonstrate that the ASC-1 complex (ASCC), which was previously shown to promote the dissociation of colliding 80S ribosomes, associates with scanning ribosomes to regulate translation initiation. Selective translation complex profiling (TCP-seq) analysis revealed that ASCC3, a helicase domain-containing subunit of ASCC, localizes predominantly to the 5' untranslated region of mRNAs. Ribo-seq, TCP-seq, and luciferase reporter analyses showed that ASCC3 knockdown impairs 43S preinitiation complex loading and scanning dynamics, thereby reducing translation efficiency. Whereas eIF4A, an RNA helicase in the eIF4F complex, is important for global translation, ASCC was found to regulate the scanning process for a specific subset of transcripts. Our results have thus revealed that ASCC is required not only for dissociation of colliding 80S ribosomes but also for efficient translation initiation by scanning ribosomes at a subset of transcripts.

Keywords: ASCC; Sel-TCP-MS; eIF4A; scanning ribosome; translation initiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Codon, Initiator
  • Eukaryotic Initiation Factor-4F* / genetics
  • Eukaryotic Initiation Factor-4F* / metabolism
  • Peptide Chain Initiation, Translational
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomes* / genetics
  • Ribosomes* / metabolism


  • Eukaryotic Initiation Factor-4F
  • 5' Untranslated Regions
  • RNA, Messenger
  • Codon, Initiator

Associated data

  • GEO/GSE186502