CDKAL1 Drives the Maintenance of Cancer Stem-Like Cells by Assembling the eIF4F Translation Initiation Complex

Rongsheng Huang, Takahiro Yamamoto, Eiji Nakata, Toshifumi Ozaki, Kazuhiko Kurozumi, Fanyan Wei, Kazuhito Tomizawa, Atsushi Fujimura

Research output: Contribution to journalArticlepeer-review


Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers. Translatome analysis reveals that a group of mRNAs whose translation is CDKAL1-dependent contains cytosine-rich sequences in the 5’ untranslated region (5’UTR). Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. This complex formation does not require the enzyme activity of CDKAL1 but requires only the NH2-terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for forming the eIF4F complex are identified and discovered candidate inhibitors of CDKAL1-dependent translation.

Original languageEnglish
JournalAdvanced Science
Publication statusAccepted/In press - 2023


  • cancer stem-like cells
  • CDKAL1
  • CG-rich 5’UTR
  • eIF4F complex
  • SALL2

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)


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