Early Dysregulation of RNA Splicing and Translation Processes Are Key Markers from Mild Cognitive Impairment to Alzheimer’s Disease: An In Silico Transcriptomic Analysis
Abstract
1. Introduction
2. Results
2.1. Differential Expression Analysis
2.2. DEGs Selection and Filtering
2.3. Over-Representation Analysis (ORA)
2.4. Network Analysis
3. Discussion
4. Materials and Methods
4.1. Dataset Selection
4.2. Dataset Information
4.3. Bioinformatics Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
Aβ | Amyloid beta |
FAD | AD familial form |
SAD | AD sporadic form |
MCI | Mild cognitive impairment |
CTL | Healthy controls |
CTLvsAD | Comparison among CTL and AD groups |
CTLvsMCI | Comparison among CTL and MCI groups |
DEGs | Differentially expressed genes |
FDR | False discovery rate |
FC | Fold change |
GO | Gene ontology |
ORA | Over-representation analysis |
BP | Biological process |
MF | Molecular function |
CC | Cellular component |
SSU | Small subunit |
GEO | Gene expression omnibus |
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Genes Family | Genes Included |
---|---|
EXOSC | EXOSC1, EXOSC3, EXOSC7, EXOSC8, EXOSC9 |
MRPL | MRPL1, MRPL3, MRPL13, MRPL15, MRPL17, MRPL18, MRPL21, MRPL22, MRPL24, MRPL27, MRPL32, MRPL33, MRPL35, MRPL36, MRPL39, MRPL40, MRPL42, MRPL45, MRPL46, MRPL47, MRPL48, MRPL50, MRPL51, MRPL58 |
MRPS | MRPS7, MRPS17, MRPS18C, MRPS21, MRPS22, MRPS23, MRPS28, MRPS31, MRPS33 |
RPL | RPL3, RPL4, RPL5, RPL6, RPL7, RPL11, RPL12, RPL17, RPL21, RPL23, RPL24, RPL26, RPL26L1, RPL27, RPL30, RPL31, RPL34, RPL35, RPL35A, RPL36AL, RPL39, RPL41 |
RPS | RPS3A, RPS4X, RPS6, RPS7, RPS10, RPS12, RPS13, RPS14, RPS17, RPS18, RPS20, RPS21, RPS24, RPS25, RPS27, RPS27A, RPS27L, RPS29 |
DEGs | Regulation | Function | Possible Role in Neurodegeneration | References |
---|---|---|---|---|
UTP6, UTP11, UTP14A | Downregulated | Required for SSU biogenesis and involved in nucleolar processing of pre-18 S ribosomal RNA. | Downregulation of UTP11 is observed in early stages of AD and is implicated in nucleolar stress and altered ribosomal biogenesis. | [62] |
RPF1, RPF2 | Downregulated | Involved in ribosomal large subunit assembly. | Depletion of RPF2 blocks the 27 pre-RNA-processing process, inducing nucleolar stress. | [63] |
NOP58, NOP10, DKC1 | Downregulated | Required for 60 S ribosomal subunit biogenesis. Core component of snoRNP particles. | Depletion of DKC1 and NOP10 causes increased oxidative stress and impaired ribosomal biogenesis. Both of these processes are closely implicated in the pathophysiology of neurodegenerative diseases. | [64] |
RPL30, RPL34, RPL4 | Downregulated | Component of the large ribosomal subunit. | Downregulation of these ribosomal proteins are observed in hippocampal samples from AD. | [36] |
EIF3E, EIF3M | Downregulated | Component of the eIF-3 complex, which is required for several steps in the initiation of protein synthesis. | The low expression of the factor eIF3 was observed in hippocampus samples from patients with AD. | [49] |
SNRPG, SNRPD2, SNRPF, SNRPA, SNRPB2 | Downregulated | Structural components of the protein core of the U1 snRNP complex, involved in the recognition of the 5′ splicing site. | There is no direct evidence of their downregulation in the neurodegeneration process. However, alteration of the U1 snRNP complex is associated with splicing defects in the brains of AD patients. | [65] |
PRPF18, ISY1, SLU7 | Downregulated | Factors involved in pre-RNA splicing | Involved in DNA splicing and repair (via APE1); although there is no direct evidence in neurodegeneration, its downregulation may reduce the response to genotoxic damage. | [66] |
GEMIN6, GEMIN2 | Downregulated | The SMN complex catalyzes the assembly of snRNPs, the components of spliceosome. | The SMN complex deficit may contribute to SMA and neuronal splicing dysfunctions and neurodegeneration. | [67] |
LTO1 | Upregulated | Required for biogenesis of the large ribosomal subunit and initiation of translation. | The upregulation, although not directly associated with neurodegeneration, could reflect a compensatory mechanism against oxidative stress, one of the mechanisms relevant in neurodegenerative diseases. | [40] |
Sample Groups | Age Mean | Sex Distribution |
---|---|---|
CTL | 72.4 ± 6.3 | 42 M 62 F |
MCI | 74.5 ± 6.0 | 41 M 39 F |
AD | 75.4 ± 6.6 | 46 M 99 F |
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D’Angiolini, S.; Gugliandolo, A.; Calì, G.; Chiricosta, L. Early Dysregulation of RNA Splicing and Translation Processes Are Key Markers from Mild Cognitive Impairment to Alzheimer’s Disease: An In Silico Transcriptomic Analysis. Int. J. Mol. Sci. 2025, 26, 7303. https://doi.org/10.3390/ijms26157303
D’Angiolini S, Gugliandolo A, Calì G, Chiricosta L. Early Dysregulation of RNA Splicing and Translation Processes Are Key Markers from Mild Cognitive Impairment to Alzheimer’s Disease: An In Silico Transcriptomic Analysis. International Journal of Molecular Sciences. 2025; 26(15):7303. https://doi.org/10.3390/ijms26157303
Chicago/Turabian StyleD’Angiolini, Simone, Agnese Gugliandolo, Gabriella Calì, and Luigi Chiricosta. 2025. "Early Dysregulation of RNA Splicing and Translation Processes Are Key Markers from Mild Cognitive Impairment to Alzheimer’s Disease: An In Silico Transcriptomic Analysis" International Journal of Molecular Sciences 26, no. 15: 7303. https://doi.org/10.3390/ijms26157303
APA StyleD’Angiolini, S., Gugliandolo, A., Calì, G., & Chiricosta, L. (2025). Early Dysregulation of RNA Splicing and Translation Processes Are Key Markers from Mild Cognitive Impairment to Alzheimer’s Disease: An In Silico Transcriptomic Analysis. International Journal of Molecular Sciences, 26(15), 7303. https://doi.org/10.3390/ijms26157303