RNA helicase EIF4A1-mediated translation is essential for the GC response

Michael Screen (Lead / Corresponding author), Louise S. Matheson, Andrew J. M. Howden, Douglas Strathdee, Anne E. Willis, Martin Bushell, Owen Sansom, Martin Turner (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

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Abstract

EIF4A1 and cofactors EIF4B and EIF4H have been well characterised in cancers, including B cell malignancies, for their ability to promote the translation of oncogenes with structured 5' untranslated regions. However, very little is known of their roles in nonmalignant cells. Using mouse models to delete Eif4a1, Eif4b or Eif4h in B cells, we show that EIF4A1, but not EIF4B or EIF4H, is essential for B cell development and the germinal centre response. After B cell activation in vitro, EIF4A1 facilitates an increased rate of protein synthesis, MYC expression, and expression of cell cycle regulators. However, EIF4A1-deficient cells remain viable, whereas inhibition of EIF4A1 and EIF4A2 by Hippuristanol treatment induces cell death.

Original languageEnglish
Article numbere202302301
Number of pages12
JournalLife Science Alliance
Volume7
Issue number2
Early online date27 Nov 2023
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Animals
  • Mice
  • Eukaryotic Initiation Factor-4A/genetics
  • RNA Helicases/metabolism
  • B-Lymphocytes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Health, Toxicology and Mutagenesis
  • Plant Science
  • Ecology

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