Phosphorylation of ribosomal protein S6 differentially affects mRNA translation based on ORF length

Bohlen, Jonathan; Roiuk, Mykola; Teleman, Aurelio A.

doi:10.1093/nar/gkab1157

Cited by 48 publications

(43 citation statements)

References 35 publications

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“…Among those, however, an exception is that of 5TOP mRNAs that mainly encode ribosomal proteins and are translated more efficiently in S6 −/−P than WT cells. In agreement with this observation, ribosomal protein levels, a proxy of ribosome content, are higher in S6 −/−P as compared to WT cell (Bohlen et al, 2021), which is consistent with the difference in the rates of protein synthesis (Ruvinsky et al, 2005). An in vivo study employing S6 P−/mice indicates that in liver of animals fed after fasting eS6 phosphorylation mediates in part the stimulatory effects of S6K on the transcription of genes encoding RiBi (ribosome biogenesis) factors, implicated in the assembly and maturation of ribosomal subunits, contributing therefore to the increase in ribosome synthesis that ensues in response to feeding (Chauvin et al, 2014).…”

Section: Protein Synthesissupporting

confidence: 83%

“…The mechanistic aspects of these effects have not been thoroughly investigated and it cannot be excluded that they arise from the activation of compensatory mechanisms. Some clues come from a recent study that by comparing the translation efficiency of WT and S6 −/−P cells provides evidence that eS6 phosphorylation has a mild stimulatory effect on the translation of short mRNAs (Bohlen et al, 2021). Among those, however, an exception is that of 5TOP mRNAs that mainly encode ribosomal proteins and are translated more efficiently in S6 −/−P than WT cells.…”

Section: Protein Synthesismentioning

confidence: 99%

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S6 kinase 1 at the central node of cell size and ageing

Fumagalli

Pende

2022

Front. Cell Dev. Biol.

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Genetic evidence in living organisms from yeast to plants and animals, including humans, unquestionably identifies the Target Of Rapamycin kinase (TOR or mTOR for mammalian/mechanistic) signal transduction pathway as a master regulator of growth through the control of cell size and cell number. Among the mTOR targets, the activation of p70 S6 kinase 1 (S6K1) is exquisitely sensitive to nutrient availability and rapamycin inhibition. Of note, in vivo analysis of mutant flies and mice reveals that S6K1 predominantly regulates cell size versus cell proliferation. Here we review the putative mechanisms of S6K1 action on cell size by considering the main functional categories of S6K1 targets: substrates involved in nucleic acid and protein synthesis, fat mass accumulation, retrograde control of insulin action, senescence program and cytoskeleton organization. We discuss how S6K1 may be involved in the observed interconnection between cell size, regenerative and ageing responses.

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Section: Protein Synthesissupporting

confidence: 83%

Section: Protein Synthesismentioning

confidence: 99%

S6 kinase 1 at the central node of cell size and ageing

Fumagalli

Pende

2022

Front. Cell Dev. Biol.

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“…General events in these pathways include: (1) phosphorylation of eIF2a; (2) phosphorylation of eIF4E-binding proteins; (3) phosphorylation of ribosomal protein S6; (4) inosine modification of double-stranded RNA; (5) endonucleolytic cleavage of ribosomal RNA. Combinations of these stress-activated inhibitory pathways play a major role in reprogramming protein translation in stressed cells [ 6 , 7 , 8 , 9 , 10 ]. Mechanisms of stress-induced protein synthesis inhibition also include the targeting of RNA components of the translational machinery—tRNAs in particular—by specific ribonucleases (RNases).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Recombinant Human Angiogenin in Keratinocytes: New Insights on Oxidative Stress Response Mediated by RNases

Culurciello

Bosso

Troisi

et al. 2022

IJMS

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Human angiogenin (ANG) is a 14-kDa ribonuclease involved in different pathophysiological processes including tumorigenesis, neuroprotection, inflammation, innate immunity, reproduction, the regeneration of damaged tissues and stress cell response, depending on its intracellular localization. Under physiological conditions, ANG moves to the cell nucleus where it enhances rRNA transcription; conversely, recent reports indicate that under stress conditions, ANG accumulates in the cytoplasmic compartment and modulates the production of tiRNAs, a novel class of small RNAs that contribute to the translational inhibition and recruitment of stress granules (SGs). To date, there is still limited and controversial experimental evidence relating to a hypothetical role of ANG in the epidermis, the outermost layer of human skin, which is continually exposed to external stressors. The present study collects compelling evidence that endogenous ANG is able to modify its subcellular localization on HaCaT cells, depending on different cellular stresses. Furthermore, the use of recombinant ANG allowed to determine as this special enzyme is effectively able to counter at various levels the alterations of cellular homeostasis in HaCaT cells, actually opening a new vision on the possible functions that this special enzyme can support also in the stress response of human skin.

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“…However, RPS6 phosphorylation-mediated control of protein synthesis is still under debate, and may be cell type-dependent. Furthermore, Bohlen and colleagues have demonstrated that the level of RPS6 phosphorylation differentially affects mRNA translation based on the length of their coding sequence (CDS) [33]. As ribosomes translate mRNAs, RPS6 are progressively dephosphorylated.…”

Section: Discussionmentioning

confidence: 99%

The RSK-RPS6 Axis Controls the Preconditioning Effect and Induces Spinal Cord Regeneration

Decourt

Schaeffer

Blot

et al. 2022

Preprint

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Unlike immature neurons and neurons from the peripheral nervous system (PNS), mature neurons from the central nervous system (CNS) cannot regenerate after injury. In the past 15 years, huge progress has been made to identify molecules and pathways necessary for neuroprotection and/or regeneration after CNS injury. In most regenerative models, phosphorylated ribosomal protein S6 (p-S6) is upregulated in neurons, which is often associated with an activation of the mTOR pathway. However, the exact contribution of post-translational modifications of this ribosomal protein in CNS regeneration remains elusive. In this study, we demonstrate that RPS6 phosphorylation is essential for PNS and CNS regeneration. We show that this phosphorylation is induced during the preconditioning effect in dorsal root ganglion (DRG) neurons, and that it is controlled by the p90S6 kinase RSK2. Our results reveal that RSK2 controls the preconditioning effect and that the RSK2-RPS6 axis is key for this process, as well as for PNS regeneration. Finally, we demonstrate that RSK2 promotes CNS regeneration in the dorsal column and allows functional recovery. Our data establish the critical role of RPS6 phosphorylation controlled by RSK2 in CNS regeneration and give new insights into the mechanism related to axon growth and circuit formation after traumatic lesion.

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Phosphorylation of ribosomal protein S6 differentially affects mRNA translation based on ORF length

Cited by 48 publications

References 35 publications

S6 kinase 1 at the central node of cell size and ageing

S6 kinase 1 at the central node of cell size and ageing

Protective Effects of Recombinant Human Angiogenin in Keratinocytes: New Insights on Oxidative Stress Response Mediated by RNases

The RSK-RPS6 Axis Controls the Preconditioning Effect and Induces Spinal Cord Regeneration

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