Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain
The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Non-Coding RNA |
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| Online Access: | https://www.mdpi.com/2311-553X/9/1/3 |
| _version_ | 1797618968845877248 |
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| author | Allison Kirchner Fabien Dachet Leonard Lipovich Jeffrey A. Loeb |
| author_facet | Allison Kirchner Fabien Dachet Leonard Lipovich Jeffrey A. Loeb |
| author_sort | Allison Kirchner |
| collection | DOAJ |
| description | The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy. |
| first_indexed | 2024-03-11T08:20:08Z |
| format | Article |
| id | doaj.art-af5bac4ad59c4695a055eb78fd7f4a4c |
| institution | Directory Open Access Journal |
| issn | 2311-553X |
| language | English |
| last_indexed | 2024-03-11T08:20:08Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Non-Coding RNA |
| spelling | doaj.art-af5bac4ad59c4695a055eb78fd7f4a4c2023-11-16T22:28:55ZengMDPI AGNon-Coding RNA2311-553X2023-01-0191310.3390/ncrna9010003Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic BrainAllison Kirchner0Fabien Dachet1Leonard Lipovich2Jeffrey A. Loeb3Department of Neurology and Rehabilitation, University of Illinois at Chicago, 912 S Wood Street, Chicago, IL 60612, USADepartment of Neurology and Rehabilitation, University of Illinois at Chicago, 912 S Wood Street, Chicago, IL 60612, USADepartment of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai 505055, United Arab EmiratesDepartment of Neurology and Rehabilitation, University of Illinois at Chicago, 912 S Wood Street, Chicago, IL 60612, USAThe human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy.https://www.mdpi.com/2311-553X/9/1/3MAPK signalingepilepsyinteractomeevolutionlncRNA |
| spellingShingle | Allison Kirchner Fabien Dachet Leonard Lipovich Jeffrey A. Loeb Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain Non-Coding RNA MAPK signaling epilepsy interactome evolution lncRNA |
| title | Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain |
| title_full | Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain |
| title_fullStr | Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain |
| title_full_unstemmed | Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain |
| title_short | Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain |
| title_sort | activity dependent non coding rna mapk interactome of the human epileptic brain |
| topic | MAPK signaling epilepsy interactome evolution lncRNA |
| url | https://www.mdpi.com/2311-553X/9/1/3 |
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