eIF4F is a thermo-sensing regulatory node in the translational heat shock response.

Autor:	Desroches Altamirano C; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Kang MK; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Jordan MA; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany., Borianne T; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Dilmen I; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Gnädig M; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., von Appen A; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany., Honigmann A; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Franzmann TM; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany., Alberti S; Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany. Electronic address: simon.alberti@tu-dresden.de.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 May 02; Vol. 84 (9), pp. 1727-1741.e12. Date of Electronic Publication: 2024 Mar 27.
DOI:	10.1016/j.molcel.2024.02.038
Abstrakt:	Heat-shocked cells prioritize the translation of heat shock (HS) mRNAs, but the underlying mechanism is unclear. We report that HS in budding yeast induces the disassembly of the eIF4F complex, where eIF4G and eIF4E assemble into translationally arrested mRNA ribonucleoprotein particles (mRNPs) and HS granules (HSGs), whereas eIF4A promotes HS translation. Using in vitro reconstitution biochemistry, we show that a conformational rearrangement of the thermo-sensing eIF4A-binding domain of eIF4G dissociates eIF4A and promotes the assembly with mRNA into HS-mRNPs, which recruit additional translation factors, including Pab1p and eIF4E, to form multi-component condensates. Using extracts and cellular experiments, we demonstrate that HS-mRNPs and condensates repress the translation of associated mRNA and deplete translation factors that are required for housekeeping translation, whereas HS mRNAs can be efficiently translated by eIF4A. We conclude that the eIF4F complex is a thermo-sensing node that regulates translation during HS. Competing Interests: Declaration of interests S.A. is an advisor on the scientific advisory board of Dewpoint Therapeutics. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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