| Attribute | Value |
|----------|-------|
| Symbol | RPS23 |
| Name | Ribosomal Protein S23 |
| Chromosome | 5q14.1 |
| NCBI Gene ID | 6209 |
| Ensembl ID | ENSG00000130712 |
| UniProt ID | P62266 |
| Gene Type | Protein coding |
| Strand | Minus (−) |
RPS23 (Ribosomal Protein S23) encodes a ribosomal protein that is a fundamental component of the small (40S) ribosomal subunit. RPS23 is one of the most evolutionarily conserved ribosomal , with homologs found in all domains of life, reflecting its essential role in protein synthesis 1.
The human RPS23 gene is located on chromosome 5q14.1 and encodes a protein of 143 amino acids with a molecular weight of approximately 16.6 kDa. Like other ribosomal , RPS23 is essential for cell viability, and knockout of RPS23 is embryonic lethal in mice 2.
¶ Protein Structure and Function
RPS23 is located in the 40S ribosomal subunit, specifically in the platform region that interacts with the mRNA channel. The protein participates in the binding of mRNA and the initiation factor complex during translation. The protein contains a conserved S23 domain that is characteristic of ribosomal involved in RNA binding 3.
Key structural features include:
- rRNA binding domain: Interacts with 18S rRNA
- mRNA channel interface: Positions mRNA for translation
- Initiation factor binding sites: Interacts with eIF1 and eIF3
RPS23 performs several critical molecular functions:
-
Structural Constituent of Ribosome: RPS23 is an essential structural component of the 40S subunit, contributing to ribosome architecture and function 4.
-
mRNA Binding: RPS23 participates in the binding and positioning of mRNA on the ribosome, facilitating the scanning process for translation start site selection 5.
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Translation Initiation: RPS23 is involved in the formation of the pre-initiation complex (PIC) and helps coordinate the assembly of initiation factors 6.
-
Accuracy in Translation: RPS23 contributes to the fidelity of translation by ensuring proper codon-anticodon pairing 7.
RPS16 is expressed ubiquitously across all human tissues with particularly high expression in:
- Brain: Cerebral cortex, hippocampus, cerebellum
- Testis: High expression in spermatogenic cells
- Heart: Cardiac muscle tissue
- Liver: Hepatocytes
In neurons, RPS23 is localized to:
- Cell body (soma)
- Dendrites and dendritic spines
- Axon terminals
- Synaptic compartments
This neuronal distribution supports the critical role of local translation at synapses 8.
¶ Synaptic Plasticity and Memory
Neurons require precise control of protein synthesis for synaptic plasticity, the cellular basis of learning and memory. RPS23-containing ribosomes support:
- Long-term potentiation (LTP): Protein synthesis-dependent enhancement of synaptic strength
- Long-term depression (LTD): Protein synthesis-dependent weakening of synapses
- Synaptic scaling: Homeostatic adjustments in synaptic strength
- Memory consolidation: Stable changes in synaptic strength
Synaptic ribosomes, including those containing RPS23, enable rapid localized protein synthesis near synapses. This is critical for:
- Activity-dependent translation: Immediate responses to synaptic activity
- Synapse-specific protein synthesis: Targeting to specific synaptic sites
- Retrograde signaling: Presynaptic protein synthesis for signaling
RPS23 in axonal ribosomes supports:
- Axon guidance: Local translation of guidance cue receptors
- Regeneration: Axonal protein synthesis after injury
- Synapse formation: Presynaptic protein synthesis
RPS23 participates in ribosome quality control :
- Ribosome assembly surveillance: Ensuring proper 40S subunit formation
- Non-stop decay: Degradation of ribosomes stalled on incomplete mRNAs
- No-go decay: Clearance of ribosomes stalled during elongation
RPS23 has several connections to Alzheimer's disease pathology:
-
Ribosomal Dysfunction: AD brains show widespread ribosomal dysfunction with decreased expression of ribosomal , including RPS23. Post-mortem studies reveal reduced RPS23 levels in the prefrontal cortex and hippocampus of AD patients 9.
-
Translation Deficits: Global translation is impaired in AD, particularly at synapses. RPS23 function is compromised by tau pathology and amyloid-beta toxicity.
-
Synaptic Ribosome Loss: The density of synaptic ribosomes is reduced in AD, contributing to impaired local translation and synaptic dysfunction.
-
Stress Granules: In AD, RPS23 can be sequestered into stress granules, removing it from active translation.
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ER Stress: Chronic ER stress in AD affects ribosomal function and RPS23 availability.
RPS23 involvement in Parkinson's disease includes:
-
Dopaminergic Neuron Vulnerability: RPS23 expression is altered in the substantia nigra pars compacta of PD patients, where dopaminergic neurons are selectively lost.
-
Alpha-Synuclein Toxicity: Alpha-synuclein aggregation can interfere with ribosomal function, potentially affecting RPS23.
-
Mitochondrial Dysfunction: The interaction between mitochondrial stress and ribosomal function in PD may involve RPS23.
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LRRK2 Pathogenesis: Mutations in LRRK2 (a common genetic cause of PD) affect translation, potentially involving ribosomal .
RPS23 mutations are associated with ribosomopathies — characterized by ribosomal dysfunction:
-
Diamond-Blackfan Anemia (DBA): While most commonly associated with RPS19 and RPS24, RPS23 variants can cause DBA, a bone marrow failure syndrome 10.
-
5q- Syndrome: A deletion syndrome involving the RPS23 region causes macrocytic anemia and other hematological abnormalities.
-
T-Cell Acute Lymphoblastic Leukemia: RPS23 is occasionally involved in chromosomal translocations in T-ALL.
RPS23 dysregulation is observed in multiple cancers:
- Breast cancer: Overexpression associated with poor prognosis
- Colorectal cancer: RPS23 promotes tumor growth via enhanced translation
- Lung cancer: RPS23 levels correlate with proliferation and metastasis
- Glioblastoma: RPS23 contributes to aggressive tumor behavior
RPS23 variants have been reported in:
- Autism spectrum disorder
- Intellectual disability
- Developmental delay
Common SNPs in RPS23 have been studied for:
- Cancer susceptibility variants
- Drug response predictions
- Neurological trait associations
Rare loss-of-function variants in RPS23 cause:
- Ribosomal deficiency
- Developmental abnormalities
- Increased cancer risk
RPS23 interacts with other 40S ribosomal :
- RPS2, RPS3, RPS4X, RPS5, RPS6, RPS7, RPS8, RPS9, RPS10
- RPS11, RPS12, RPS13, RPS14, RPS15, RPS16, RPS17, RPS18, RPS19, RPS20
- RPS21, RPS22, RPS24, RPS25, RPS26, RPS27, RPS27L, RPS28, RPS29
- EIF1 (SUI1): Start codon recognition
- EIF1A: Translation initiation factor
- EIF3 complex: Large initiation factor complex
- EIF2: GTPase for Met-tRNAiMet delivery
- Stress granule components
- Ribosome-associated quality control factors
- RNA binding
RPS23 is involved in the cellular response to various stresses:
- Oxidative stress: RPS23 modification under oxidative conditions
- Heat shock: Stress granule formation sequesters RPS23
- UV irradiation: RPS23 participates in translation shutdown
Ribosome profiling studies in neurodegenerative disease models have revealed:
- Altered translation efficiency: Specific mRNAs show changed ribosome occupancy
- Synaptic translation deficits: Reduced translation of synaptic
- Global slowdown: Reduced translation rates affect RPS23-containing ribosomes
RPS23 contributes to translation fidelity through:
- Proofreading at the decoding center
- Monitoring codon-anticodon interactions
- Participating in ribosomal quality control
Understanding RPS23 function has led to potential therapeutic strategies:
- Translation enhancers: Small molecules to improve ribosomal function
- Ribosome protectors: Preventing ribosomal stress-induced dysfunction
- Synapse-targeted therapies: Enhancing local translation
- Biomarkers: RPS23 levels as indicators of ribosomal health
flowchart TD
subgraph Initiation
A["40S Ribosome<br/>with RPS23"]:::blue --> B["mRNA<br/>Binding"]:::blue
B --> C["5'UTR<br/>Scanning"]:::blue
C --> D["Start Codon<br/>Selection"]:::orange
D --> E["60S Subunit<br/>Joining"]:::green
end
subgraph Elongation
E --> F["Codon<br/>Reading"]:::green
F --> G["Peptide Bond<br/>Formation"]:::green
G --> H["Translocation<br/>Ribosome"]:::green
H --> I["Translation<br/>Termination"]:::green
end
subgraph Quality_Control
J["Stalled<br/>Ribosome"]:::orange --> K{"Error Type"}:::yellow
K -->|"Non-stop"| L["Ribosome<br/>Rescue"]:::orange
K -->|"No-go"| M["Collision<br/>Detection"]:::orange
K -->|"Misincorporated"| N["Translational<br/>Editing"]:::orange
end
A --> J
E --> F
I --> A
classDef blue fill:#e1f5fe,stroke:#333
classDef orange fill:#fff3e0,stroke:#333
classDef yellow fill:#fff9c4,stroke:#333
classDef green fill:#c8e6c9,stroke:#333
click A "//rps23-protein" "RPS23 Protein"
click B "//translation-initiation" "Translation Initiation"
click J "//ribosome-quality-control" "Ribosome Quality Control"
click K "//ribosome-quality-control" "Ribosome Quality Control"
flowchart LR
subgraph Normal_Function
A["RPS23 + 40S<br/>Ribosome"]:::green --> B["Normal<br/>Translation"]:::green
B --> C["Synaptic<br/>Function"]:::green
C --> D["Neuronal<br/>Health"]:::green
end
subgraph AD_Pathology
E["Amyloid-beta<br/>Oligomers"]:::red --> F["Ribosomal<br/>Dysfunction"]:::red
F --> G["RPS23<br/>Depletion"]:::red
G --> H["Translation<br/>Deficit"]:::red
H --> I["Synaptic<br/>Loss"]:::red
I --> J["Neuronal<br/>Death"]:::red
end
subgraph PD_Pathology
K["Alpha-synuclein<br/>Aggregation"]:::red --> L["ER<br/>Stress"]:::red
L --> M["Ribosomal<br/>Inhibition"]:::red
M --> N["RPS23<br/>Sequestration"]:::red
N --> O["Dopaminergic<br/>Neuron Death"]:::red
end
A -.->|Disrupted| E
A -.->|Disrupted| K
classDef blue fill:#e1f5fe,stroke:#333
classDef green fill:#c8e6c9,stroke:#333
classDef red fill:#ffcdd2,stroke:#333
click A "/genes/rps23" "RPS23 Gene"
click B "//translation" "Protein Translation"
click E "//amyloid-beta" "Amyloid-beta"
click K "//alpha-synuclein" "Alpha-Synuclein"
click J "//alzheimers-disease" "Alzheimer's Disease"
click O "//parkinsons-disease" "Parkinson's Disease"
- RPS23 — Protein page
- RPS16 — Structurally related
- RPS19 — DBA-associated
- RPS24 — DBA-associated
- Ribosome Biogenesis — 40S assembly
- Translation Initiation — Initiation factors
- Synaptic Plasticity — Protein synthesis
- Ribosome Quality Control — Quality surveillance
- Alzheimer's Disease
- Parkinson's Disease
- Diamond-Blackfan Anemia
- Ribosomopathies
- Allen Human Brain Atlas*: Gene expression search
- [Allen Mouse Brain Atlas*: Gene search
- Allen Cell Type Atlas: Transcriptomic cell type reference
- BrainSpan Developmental Transcriptome: Developmental expression