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. 2022 Oct 6:9:1008921.
doi: 10.3389/fmolb.2022.1008921. eCollection 2022.

Are there roles for heterogeneous ribosomes during sleep in the rodent brain?

Isla M Buchanan  1 , Trevor M Smith  2   3 , André P Gerber  2 , Julie Seibt  3
Affiliations

Are there roles for heterogeneous ribosomes during sleep in the rodent brain?

Isla M Buchanan et al. Front Mol Biosci. .

Abstract

The regulation of mRNA translation plays an essential role in neurons, contributing to important brain functions, such as brain plasticity and memory formation. Translation is conducted by ribosomes, which at their core consist of ribosomal proteins (RPs) and ribosomal RNAs. While translation can be regulated at diverse levels through global or mRNA-specific means, recent evidence suggests that ribosomes with distinct configurations are involved in the translation of different subsets of mRNAs. However, whether and how such proclaimed ribosome heterogeneity could be connected to neuronal functions remains largely unresolved. Here, we postulate that the existence of heterologous ribosomes within neurons, especially at discrete synapses, subserve brain plasticity. This hypothesis is supported by recent studies in rodents showing that heterogeneous RP expression occurs in dendrites, the compartment of neurons where synapses are made. We further propose that sleep, which is fundamental for brain plasticity and memory formation, has a particular role in the formation of heterologous ribosomes, specialised in the translation of mRNAs specific for synaptic plasticity. This aspect of our hypothesis is supported by recent studies showing increased translation and changes in RP expression during sleep after learning. Thus, certain RPs are regulated by sleep, and could support different sleep functions, in particular brain plasticity. Future experiments investigating cell-specific heterogeneity in RPs across the sleep-wake cycle and in response to different behaviour would help address this question.

Keywords: brain plasticity; neurites; neuron; ribosomal protein; ribosome heterogeneity; sleep; synapse.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Sources and effect of ribosomal heterogeneity in neurons. (A) Morphology of a neuron. i) Schematic of a neuron showing the cell body, dendrites and axon. ii) Close-up schematic of dendrites with ribosomes shown as green dots located both in and adjacent to synapses. iii) Close-up schematic of the synapse with ribosomes shown as green dots in the cytoplasm in both the post-synaptic neuron (i.e., spine in purple) and pre-synaptic neuron (i.e., axon terminal in blue). (B) Structure of the ribosome with the large subunit (green), small subunit (blue), ribosomal RNA (rRNA in orange), and messenger RNA (mRNA in black). For the large and small subunit, the different colours indicate different ribosomal proteins. (C) Schematic showing six sources of ribosomal variation, with illustrative examples of how these changes manifest: i) RP paralogs, ii) RP stoichiometry, iii) Ribosomal associated factors, iv) RP modification, v) rRNA variation, and vi) rRNA modification (adapted from (Norris et al., 2021)). Created with BioRender.com.
FIGURE 2
FIGURE 2
Contribution of RPs to ribosome heterogeneity in neurons and functional significance. (A) Table indicating the presence (green check mark) or absence of select RP (top line) mRNAs in whole neurons vs. dendrites or axons, according to previous studies (Poulopoulos et al., 2019; Biever et al., 2020; Perez et al., 2021a). RP location (non-surface: grey boxes; surface: blue boxes) was determined using human ribosome structure (PDB: 4V6X). (B) Heatmap (Morpheus, https://software.broadinstitute.org/morpheus) representing heterogeneous expression of selected RPs in neurons from in vivo studies in rodents or in vitro studies. The colour bar depicts log (2) fold changes (FC) of the particular conditions (indicated on the left) against control condition values (see D and (Rozenbaum et al., 2018; Lyons et al., 2020; Delorme et al., 2021; Fusco et al., 2021) for experimental details). From top to bottom: 1) 13 RP transcripts on membrane-bound ribosomes in activated (pS6+) neurons in the hippocampus following contextual fear conditioning and subsequent sleep in mice (Delorme et al., 2021). 2) 7 RP mRNAs affected by acute (5 h) sleep deprivation in excitatory neurons (CamKIIα+) in the mouse hippocampus (Lyons et al., 2020). 3) The five largest changes for small and large ribosomal subunits (10 RPs) in dorsal root ganglion (DRG) neurons following sciatic nerve injury, 4 h after injury (Rozenbaum et al., 2018). 4) 5 RPs that are significantly upregulated after 0.1 mM H2O2 treatment of primary neuronal culture; values are average of three biological replicates (Fusco et al., 2021). Additionally, log (2)FC values for RPs previously mentioned in the text and associated with ribosome specialisation (RPS19, RPS25, RPL10A and RPL38) were included for each study if they were present in the original data. (C,D) Schematic experimental approaches of the studies performed in neuronal compartments (C) relates to (A) and functional assays (D) relates to (B). The blue boxes specify the type of analysis performed for each study for data visualisation. Created with BioRender.com.
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