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Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance

Author

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  • Patrick R. Smith

    (The University of Texas at Dallas, Department of Biological Sciences)

  • Sarah Loerch

    (Janelia Research Campus, Howard Hughes Medical Institute
    University of California, Santa Cruz, Department of Chemistry and Biochemistry)

  • Nikesh Kunder

    (The University of Texas at Dallas, Department of Biological Sciences)

  • Alexander D. Stanowick

    (The University of Texas at Dallas, Department of Biological Sciences)

  • Tzu-Fang Lou

    (The University of Texas at Dallas, Department of Biological Sciences)

  • Zachary T. Campbell

    (The University of Texas at Dallas, Department of Biological Sciences
    The Center for Advanced Pain Studies (CAPS), University of Texas at Dallas)

Abstract

Processing bodies (p-bodies) are a prototypical phase-separated RNA-containing granule. Their abundance is highly dynamic and has been linked to translation. Yet, the molecular mechanisms responsible for coordinate control of the two processes are unclear. Here, we uncover key roles for eEF2 kinase (eEF2K) in the control of ribosome availability and p-body abundance. eEF2K acts on a sole known substrate, eEF2, to inhibit translation. We find that the eEF2K agonist nelfinavir abolishes p-bodies in sensory neurons and impairs translation. To probe the latter, we used cryo-electron microscopy. Nelfinavir stabilizes vacant 80S ribosomes. They contain SERBP1 in place of mRNA and eEF2 in the acceptor site. Phosphorylated eEF2 associates with inactive ribosomes that resist splitting in vitro. Collectively, the data suggest that eEF2K defines a population of inactive ribosomes resistant to recycling and protected from degradation. Thus, eEF2K activity is central to both p-body abundance and ribosome availability in sensory neurons.

Suggested Citation

  • Patrick R. Smith & Sarah Loerch & Nikesh Kunder & Alexander D. Stanowick & Tzu-Fang Lou & Zachary T. Campbell, 2021. "Functionally distinct roles for eEF2K in the control of ribosome availability and p-body abundance," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27160-4
    DOI: 10.1038/s41467-021-27160-4
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    1. Anita E. Autry & Megumi Adachi & Elena Nosyreva & Elisa S. Na & Maarten F. Los & Peng-fei Cheng & Ege T. Kavalali & Lisa M. Monteggia, 2011. "NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses," Nature, Nature, vol. 475(7354), pages 91-95, July.
    2. Andreas M. Anger & Jean-Paul Armache & Otto Berninghausen & Michael Habeck & Marion Subklewe & Daniel N. Wilson & Roland Beckmann, 2013. "Structures of the human and Drosophila 80S ribosome," Nature, Nature, vol. 497(7447), pages 80-85, May.
    3. Marcello Ceci & Cristina Gaviraghi & Chiara Gorrini & Leonardo A. Sala & Nina Offenhäuser & Pier Carlo Marchisio & Stefano Biffo, 2003. "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly," Nature, Nature, vol. 426(6966), pages 579-584, December.
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    1. Patrick C. Hoffmann & Jan Philipp Kreysing & Iskander Khusainov & Maarten W. Tuijtel & Sonja Welsch & Martin Beck, 2022. "Structures of the eukaryotic ribosome and its translational states in situ," Nature Communications, Nature, vol. 13(1), pages 1-9, December.

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