PMID- 36786012
OWN - NLM
STAT- MEDLINE
DCOM- 20230427
LR  - 20230919
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 10
IP  - 12
DP  - 2023 Apr
TI  - CDKAL1 Drives the Maintenance of Cancer Stem-Like Cells by Assembling the eIF4F 
      Translation Initiation Complex.
PG  - e2206542
LID - 10.1002/advs.202206542 [doi]
LID - 2206542
AB  - 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 
      NH(2) -terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for 
      forming the eIF4F complex are identified and discovered candidate inhibitors of 
      CDKAL1-dependent translation.
CI  - (c) 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Huang, Rongsheng
AU  - Huang R
AD  - Department of Cellular Physiology, Okayama University Graduate School of 
      Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, 700-8558, 
      Japan.
FAU - Yamamoto, Takahiro
AU  - Yamamoto T
AD  - Department of Molecular Physiology, Kumamoto University Faculty of Life Sciences, 
      Kumamoto, Kumamoto, 860-0811, Japan.
FAU - Nakata, Eiji
AU  - Nakata E
AD  - Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, 
      Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, 700-8558, Japan.
FAU - Ozaki, Toshifumi
AU  - Ozaki T
AD  - Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, 
      Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, 700-8558, Japan.
FAU - Kurozumi, Kazuhiko
AU  - Kurozumi K
AD  - Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, 
      Shizuoka, 431-3192, Japan.
FAU - Wei, Fanyan
AU  - Wei F
AD  - Department of Modomics Biology and Medicine, Institute of Development, Aging and 
      Cancer, Tohoku University, Sendai, Miyagi, 980-8575, Japan.
FAU - Tomizawa, Kazuhito
AU  - Tomizawa K
AD  - Department of Molecular Physiology, Kumamoto University Faculty of Life Sciences, 
      Kumamoto, Kumamoto, 860-0811, Japan.
FAU - Fujimura, Atsushi
AU  - Fujimura A
AUID- ORCID: 0000-0002-8638-5460
AD  - Department of Cellular Physiology, Okayama University Graduate School of 
      Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, 700-8558, 
      Japan.
AD  - Neutron Therapy Research Center, Okayama University, Okayama, Okayama, 700-8558, 
      Japan.
LA  - eng
GR  - 18077107/Japan Agency for Medical Research and Development/
GR  - 20318557/Japan Agency for Medical Research and Development/
GR  - The Naito Foundation/
GR  - JP20K07618/Japan Society for the Promotion of Science/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230214
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - 0 (Eukaryotic Initiation Factor-4F)
RN  - 0 (RNA, Messenger)
RN  - EC 2.8.4.5 (CDKAL1 protein, human)
RN  - EC 2.1.1.- (tRNA Methyltransferases)
SB  - IM
MH  - Humans
MH  - *Eukaryotic Initiation Factor-4F/genetics/metabolism
MH  - Protein Biosynthesis/genetics
MH  - RNA, Messenger/genetics
MH  - *Neoplasms
MH  - tRNA Methyltransferases/genetics/metabolism
PMC - PMC10131790
OTO - NOTNLM
OT  - CDKAL1
OT  - CG-rich 5'UTR
OT  - SALL2
OT  - cancer stem-like cells
OT  - eIF4F complex
COIS- Atsushi Fujimura is applying a patent that might be connected to the manuscript. 
      The other authors declare that they have no competing interests.
EDAT- 2023/02/15 06:00
MHDA- 2023/04/27 06:42
PMCR- 2023/02/14
CRDT- 2023/02/14 03:33
PHST- 2023/01/06 00:00 [revised]
PHST- 2022/11/08 00:00 [received]
PHST- 2023/04/27 06:42 [medline]
PHST- 2023/02/15 06:00 [pubmed]
PHST- 2023/02/14 03:33 [entrez]
PHST- 2023/02/14 00:00 [pmc-release]
AID - ADVS5234 [pii]
AID - 10.1002/advs.202206542 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2023 Apr;10(12):e2206542. doi: 10.1002/advs.202206542. Epub 2023 
      Feb 14.