7ls1 › Citations

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

<div class='caption-title'>The translation inhibitor emetine reduces p-bodies in primary sensory neurons.</div>
<div class='caption-title'>eEF2K controls p-body numbers in sensory neurons.</div>
<div class='caption-title'>eEF2K is expressed in sensory neurons but does not localize to SNPBs.</div>
Smith PR, Loerch S, Kunder N, Stanowick AD, Lou TF, Campbell ZT
OpenAccess logo Nat Commun 12 6789 (2021)
Cited: 8 times
EuropePMC logo PMID: 34815424

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.

Reviews - 7ls1 mentioned but not cited (1)

  1. The space between notes: emerging roles for translationally silent ribosomes. Smith PR, Pandit SC, Loerch S, Campbell ZT. Trends Biochem Sci 47 477-491 (2022)


Reviews citing this publication (2)

  1. Recent advances and current trends in cryo-electron microscopy. Guaita M, Watters SC, Loerch S. Curr Opin Struct Biol 77 102484 (2022)
  2. The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies. Yue YL, Zhang MY, Liu JY, Fang LJ, Qu YQ. Ther Adv Respir Dis 16 17534666221140972 (2022)

Articles citing this publication (5)

  1. Structures of the eukaryotic ribosome and its translational states in situ. Hoffmann PC, Kreysing JP, Khusainov I, Tuijtel MW, Welsch S, Beck M. Nat Commun 13 7435 (2022)
  2. A molecular network of conserved factors keeps ribosomes dormant in the egg. Leesch F, Lorenzo-Orts L, Pribitzer C, Grishkovskaya I, Roehsner J, Chugunova A, Matzinger M, Roitinger E, Belačić K, Kandolf S, Lin TY, Mechtler K, Meinhart A, Haselbach D, Pauli A. Nature 613 712-720 (2023)
  3. Initiation of translation on nedicistrovirus and related intergenic region IRESs by their factor-independent binding to the P site of 80S ribosomes. Miścicka A, Lu K, Abaeva IS, Pestova TV, Hellen CUT. RNA 29 1051-1068 (2023)
  4. Protocol for the isolation and culture of mouse dorsal root ganglion neurons for imaging applications. Smith PR, Meyer A, Loerch S, Campbell ZT. STAR Protoc 4 102717 (2023)
  5. SpotitPy: a semi-automated tool for object-based co-localization of fluorescent labels in microscopy images. Akalestou-Clocher A, Kalamara V, Topalis P, Garinis GA. BMC Bioinformatics 23 439 (2022)


Quick links