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

Michael Screen; Louise S. Matheson; Andrew J. M. Howden; Douglas Strathdee; Anne E. Willis; Martin Bushell; Owen Sansom; Martin Turner

doi:10.26508/lsa.202302301

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)

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-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 language	English
Article number	e202302301
Number of pages	12
Journal	Life Science Alliance
Volume	7
Issue number	2
Early online date	27 Nov 2023
DOIs	https://doi.org/10.26508/lsa.202302301
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.26508/lsa.202302301Licence: CC BY

Final Published versionFinal published version, 3.02 MBLicence: CC BY

Cite this

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title = "RNA helicase EIF4A1-mediated translation is essential for the GC response",

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.",

keywords = "Animals, Mice, Eukaryotic Initiation Factor-4A/genetics, RNA Helicases/metabolism, B-Lymphocytes",

author = "Michael Screen and Matheson, {Louise S.} and Howden, {Andrew J. M.} and Douglas Strathdee and Willis, {Anne E.} and Martin Bushell and Owen Sansom and Martin Turner",

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doi = "10.26508/lsa.202302301",

language = "English",

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T1 - RNA helicase EIF4A1-mediated translation is essential for the GC response

AU - Screen, Michael

AU - Matheson, Louise S.

AU - Howden, Andrew J. M.

AU - Strathdee, Douglas

AU - Willis, Anne E.

AU - Bushell, Martin

AU - Sansom, Owen

AU - Turner, Martin

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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.

KW - Animals

KW - Mice

KW - Eukaryotic Initiation Factor-4A/genetics

KW - RNA Helicases/metabolism

KW - B-Lymphocytes

U2 - 10.26508/lsa.202302301

DO - 10.26508/lsa.202302301

M3 - Article

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SN - 2575-1077

VL - 7

JO - Life Science Alliance

JF - Life Science Alliance

IS - 2

M1 - e202302301

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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