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Popper, B.* ; Bürkle, M.* ; Ciccopiedi, G.* ; Marchioretto, M.* ; Forné, I.* ; Imhof, A.* ; Straub, T.* ; Viero, G.* ; Götz, M. ; Schieweck, R.*

Ribosome inactivation regulates translation elongation in neurons.

J. Biol. Chem. 300:105648 (2024)
DOI PMC
Creative Commons Lizenzvertrag
Cellular plasticity is crucial for adapting to ever-changing stimuli. As a result, cells consistently reshape their translatome, and, consequently, their proteome. The control of translational activity has been thoroughly examined at the stage of translation initiation. However, the regulation of ribosome speed in cells is widely unknown. In this study, we utilized a timed ribosome runoff approach along with proteomics and transmission electron microscopy, to investigate global translation kinetics in cells. We found that ribosome speeds vary amongst various cell types, such as astrocytes, induced pluripotent human stem cells, human neural stem cells, and human and rat neurons. Of all cell types studied, mature cortical neurons exhibit the highest rate of translation. This finding is particularly remarkable because mature cortical neurons express eEF2 at lower levels than other cell types. Neurons solve this conundrum by inactivating a fraction of their ribosomes. As a result, the increase in eEF2 levels leads to a reduction of inactive ribosomes and an enhancement of active ones. Processes that alter the demand for active ribosomes, like neuronal excitation, cause increased inactivation of redundant ribosomes in an eEF2-dependent manner. Our data suggest a novel regulatory mechanism in which neurons dynamically inactivate ribosomes to facilitate translational remodelling. These findings have important implications for developmental brain disorders characterised by, among other things, aberrant translation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Astrocytes ; Neuronal Stimulation ; Neurons ; Polysome Profiling ; Ribosome Speed ; Stem Cells
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: 300, Heft: 2, Seiten: , Artikelnummer: 105648 Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)