Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease
<i>FRA10AC1</i>, the causative gene for the manifestation of the <i>FRA10A</i> fragile site, encodes a well-conserved nuclear protein characterized as a non-core spliceosomal component. Pre-mRNA splicing perturbations have been linked with neurodevelopmental diseases. <i&g...
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MDPI AG
2023-02-01
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| author | Theologia Sarafidou Eleni Galliopoulou Despina Apostolopoulou Georgios A. Fragkiadakis Nicholas K. Moschonas |
| author_facet | Theologia Sarafidou Eleni Galliopoulou Despina Apostolopoulou Georgios A. Fragkiadakis Nicholas K. Moschonas |
| author_sort | Theologia Sarafidou |
| collection | DOAJ |
| description | <i>FRA10AC1</i>, the causative gene for the manifestation of the <i>FRA10A</i> fragile site, encodes a well-conserved nuclear protein characterized as a non-core spliceosomal component. Pre-mRNA splicing perturbations have been linked with neurodevelopmental diseases. <i>FRA10AC1</i> variants have been, recently, causally linked with severe neuropathological and growth retardation phenotypes. To further elucidate the participation of FRA10AC1 in spliceosomal multiprotein complexes and its involvement in neurological phenotypes related to splicing, we exploited protein–protein interaction experimental data and explored network information and information deduced from transcriptomics. We confirmed the direct interaction of FRA10AC1with ESS2, a non-core spliceosomal protein, mapped their interacting domains, and documented their tissue co-localization and physical interaction at the level of intracellular protein stoichiometries. Although FRA10AC1 and SF3B2, a major core spliceosomal protein, were shown to interact under in vitro conditions, the endogenous proteins failed to co-immunoprecipitate. A reconstruction of a comprehensive, strictly binary, protein–protein interaction network of FRA10AC1 revealed dense interconnectivity with many disease-associated spliceosomal components and several non-spliceosomal regulatory proteins. The topological neighborhood of FRA10AC1 depicts an interactome associated with multiple severe monogenic and multifactorial neurodevelopmental diseases mainly referring to spliceosomopathies. Our results suggest that FRA10AC1 involvement in pre-mRNA processing might be strengthened by interconnecting splicing with transcription and mRNA export, and they propose the broader role(s) of FRA10AC1 in cell pathophysiology. |
| first_indexed | 2024-03-11T06:30:10Z |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T06:30:10Z |
| publishDate | 2023-02-01 |
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| record_format | Article |
| series | Genes |
| spelling | doaj.art-8de86387c82d406aad5637d41f87c87c2023-11-17T11:16:23ZengMDPI AGGenes2073-44252023-02-0114356810.3390/genes14030568Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and DiseaseTheologia Sarafidou0Eleni Galliopoulou1Despina Apostolopoulou2Georgios A. Fragkiadakis3Nicholas K. Moschonas4Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, GreeceDepartment of Biochemistry and Biotechnology, University of Thessaly, Viopolis, 41500 Larissa, GreeceDepartment of Biology, University of Crete, 71500 Heraklion, GreeceDepartment of Nutrition and Dietetics Sciences, Hellenic Mediterranean University, Tripitos, 72300 Siteia, GreeceSchool of Medicine, University of Patras, 26500 Patras, Greece<i>FRA10AC1</i>, the causative gene for the manifestation of the <i>FRA10A</i> fragile site, encodes a well-conserved nuclear protein characterized as a non-core spliceosomal component. Pre-mRNA splicing perturbations have been linked with neurodevelopmental diseases. <i>FRA10AC1</i> variants have been, recently, causally linked with severe neuropathological and growth retardation phenotypes. To further elucidate the participation of FRA10AC1 in spliceosomal multiprotein complexes and its involvement in neurological phenotypes related to splicing, we exploited protein–protein interaction experimental data and explored network information and information deduced from transcriptomics. We confirmed the direct interaction of FRA10AC1with ESS2, a non-core spliceosomal protein, mapped their interacting domains, and documented their tissue co-localization and physical interaction at the level of intracellular protein stoichiometries. Although FRA10AC1 and SF3B2, a major core spliceosomal protein, were shown to interact under in vitro conditions, the endogenous proteins failed to co-immunoprecipitate. A reconstruction of a comprehensive, strictly binary, protein–protein interaction network of FRA10AC1 revealed dense interconnectivity with many disease-associated spliceosomal components and several non-spliceosomal regulatory proteins. The topological neighborhood of FRA10AC1 depicts an interactome associated with multiple severe monogenic and multifactorial neurodevelopmental diseases mainly referring to spliceosomopathies. Our results suggest that FRA10AC1 involvement in pre-mRNA processing might be strengthened by interconnecting splicing with transcription and mRNA export, and they propose the broader role(s) of FRA10AC1 in cell pathophysiology.https://www.mdpi.com/2073-4425/14/3/568spliceosomeexpression profileprotein interactomedisease-protein networkRNA in situ hybridizationprotein interactions methods |
| spellingShingle | Theologia Sarafidou Eleni Galliopoulou Despina Apostolopoulou Georgios A. Fragkiadakis Nicholas K. Moschonas Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease Genes spliceosome expression profile protein interactome disease-protein network RNA in situ hybridization protein interactions methods |
| title | Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease |
| title_full | Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease |
| title_fullStr | Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease |
| title_full_unstemmed | Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease |
| title_short | Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease |
| title_sort | reconstruction of a comprehensive interactome and experimental data analysis of fra10ac1 may provide insights into its biological role in health and disease |
| topic | spliceosome expression profile protein interactome disease-protein network RNA in situ hybridization protein interactions methods |
| url | https://www.mdpi.com/2073-4425/14/3/568 |
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