Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome
Abstract Mutations of the MECP2 gene lead to Rett syndrome (RTT), a rare developmental disease causing severe intellectual and physical disability. How the loss or defective function of MeCP2 mediates RTT is still poorly understood. MeCP2 is a global gene expression regulator, acting at transcriptio...
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| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-86114-8 |
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| author | Silvia Gioiosa Silvia Gasparini Carlo Presutti Arianna Rinaldi Tiziana Castrignanò Cecilia Mannironi |
| author_facet | Silvia Gioiosa Silvia Gasparini Carlo Presutti Arianna Rinaldi Tiziana Castrignanò Cecilia Mannironi |
| author_sort | Silvia Gioiosa |
| collection | DOAJ |
| description | Abstract Mutations of the MECP2 gene lead to Rett syndrome (RTT), a rare developmental disease causing severe intellectual and physical disability. How the loss or defective function of MeCP2 mediates RTT is still poorly understood. MeCP2 is a global gene expression regulator, acting at transcriptional and post-transcriptional levels. Little attention has been given so far to the contribution of alternative splicing (AS) dysregulation to RTT pathophysiology. To perform a comparative analysis of publicly available RNA sequencing (RNA-seq) studies and generate novel data resources for AS, we explored 100 human datasets and 130 mouse datasets from Mecp2-mutant models, processing data for gene expression and alternative splicing. Our comparative analysis across studies indicates common species-specific differentially expressed genes (DEGs) and differentially alternatively spliced (DAS) genes. Human and mouse dysregulated genes are involved in two main functional categories: cell-extracellular matrix adhesion regulation and synaptic functions, the first category more significantly enriched in human datasets. Our extensive bioinformatics study indicates, for the first time, a significant dysregulation of AS in human RTT datasets, suggesting the crucial contribution of altered RNA processing to the pathophysiology of RTT. |
| format | Article |
| id | doaj-art-8f99b47693874c0db410f84206b75f54 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8f99b47693874c0db410f84206b75f542025-01-26T12:27:34ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-86114-8Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndromeSilvia Gioiosa0Silvia Gasparini1Carlo Presutti2Arianna Rinaldi3Tiziana Castrignanò4Cecilia Mannironi5CINECA, SuperComputing Applications and Innovation DepartmentInstitute of Molecular Biology and Pathology, National Research CouncilDepartment of Biology and Biotechnology “C. Darwin”, Sapienza University of RomeDepartment of Biology and Biotechnology “C. Darwin”, Sapienza University of RomeDepartment of Ecological and Biological Sciences (DEB), University of TusciaInstitute of Molecular Biology and Pathology, National Research CouncilAbstract Mutations of the MECP2 gene lead to Rett syndrome (RTT), a rare developmental disease causing severe intellectual and physical disability. How the loss or defective function of MeCP2 mediates RTT is still poorly understood. MeCP2 is a global gene expression regulator, acting at transcriptional and post-transcriptional levels. Little attention has been given so far to the contribution of alternative splicing (AS) dysregulation to RTT pathophysiology. To perform a comparative analysis of publicly available RNA sequencing (RNA-seq) studies and generate novel data resources for AS, we explored 100 human datasets and 130 mouse datasets from Mecp2-mutant models, processing data for gene expression and alternative splicing. Our comparative analysis across studies indicates common species-specific differentially expressed genes (DEGs) and differentially alternatively spliced (DAS) genes. Human and mouse dysregulated genes are involved in two main functional categories: cell-extracellular matrix adhesion regulation and synaptic functions, the first category more significantly enriched in human datasets. Our extensive bioinformatics study indicates, for the first time, a significant dysregulation of AS in human RTT datasets, suggesting the crucial contribution of altered RNA processing to the pathophysiology of RTT.https://doi.org/10.1038/s41598-025-86114-8Rett syndromeRNA-seqGene expressionAlternative splicing |
| spellingShingle | Silvia Gioiosa Silvia Gasparini Carlo Presutti Arianna Rinaldi Tiziana Castrignanò Cecilia Mannironi Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome Scientific Reports Rett syndrome RNA-seq Gene expression Alternative splicing |
| title | Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome |
| title_full | Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome |
| title_fullStr | Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome |
| title_full_unstemmed | Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome |
| title_short | Integrated gene expression and alternative splicing analysis in human and mouse models of Rett syndrome |
| title_sort | integrated gene expression and alternative splicing analysis in human and mouse models of rett syndrome |
| topic | Rett syndrome RNA-seq Gene expression Alternative splicing |
| url | https://doi.org/10.1038/s41598-025-86114-8 |
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