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Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond
Retinitis pigmentosa (RP) is the most common inherited retinal disease characterized by progressive degeneration of photoreceptors and/or retinal pigment epithelium that eventually results in blindness. Mutations in pre-mRNA processing factors (PRPF3, 4, 6, 8, 31, SNRNP200, and RP9) have been linked...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355544/ https://www.ncbi.nlm.nih.gov/pubmed/34395430 http://dx.doi.org/10.3389/fcell.2021.700276 |
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author | Yang, Chunbo Georgiou, Maria Atkinson, Robert Collin, Joseph Al-Aama, Jumana Nagaraja-Grellscheid, Sushma Johnson, Colin Ali, Robin Armstrong, Lyle Mozaffari-Jovin, Sina Lako, Majlinda |
author_facet | Yang, Chunbo Georgiou, Maria Atkinson, Robert Collin, Joseph Al-Aama, Jumana Nagaraja-Grellscheid, Sushma Johnson, Colin Ali, Robin Armstrong, Lyle Mozaffari-Jovin, Sina Lako, Majlinda |
author_sort | Yang, Chunbo |
collection | PubMed |
description | Retinitis pigmentosa (RP) is the most common inherited retinal disease characterized by progressive degeneration of photoreceptors and/or retinal pigment epithelium that eventually results in blindness. Mutations in pre-mRNA processing factors (PRPF3, 4, 6, 8, 31, SNRNP200, and RP9) have been linked to 15–20% of autosomal dominant RP (adRP) cases. Current evidence indicates that PRPF mutations cause retinal specific global spliceosome dysregulation, leading to mis-splicing of numerous genes that are involved in a variety of retina-specific functions and/or general biological processes, including phototransduction, retinol metabolism, photoreceptor disk morphogenesis, retinal cell polarity, ciliogenesis, cytoskeleton and tight junction organization, waste disposal, inflammation, and apoptosis. Importantly, additional PRPF functions beyond RNA splicing have been documented recently, suggesting a more complex mechanism underlying PRPF-RPs driven disease pathogenesis. The current review focuses on the key RP-PRPF genes, depicting the current understanding of their roles in RNA splicing, impact of their mutations on retinal cell’s transcriptome and phenome, discussed in the context of model species including yeast, zebrafish, and mice. Importantly, information on PRPF functions beyond RNA splicing are discussed, aiming at a holistic investigation of PRPF-RP pathogenesis. Finally, work performed in human patient-specific lab models and developing gene and cell-based replacement therapies for the treatment of PRPF-RPs are thoroughly discussed to allow the reader to get a deeper understanding of the disease mechanisms, which we believe will facilitate the establishment of novel and better therapeutic strategies for PRPF-RP patients. |
format | Online Article Text |
id | pubmed-8355544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83555442021-08-12 Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond Yang, Chunbo Georgiou, Maria Atkinson, Robert Collin, Joseph Al-Aama, Jumana Nagaraja-Grellscheid, Sushma Johnson, Colin Ali, Robin Armstrong, Lyle Mozaffari-Jovin, Sina Lako, Majlinda Front Cell Dev Biol Cell and Developmental Biology Retinitis pigmentosa (RP) is the most common inherited retinal disease characterized by progressive degeneration of photoreceptors and/or retinal pigment epithelium that eventually results in blindness. Mutations in pre-mRNA processing factors (PRPF3, 4, 6, 8, 31, SNRNP200, and RP9) have been linked to 15–20% of autosomal dominant RP (adRP) cases. Current evidence indicates that PRPF mutations cause retinal specific global spliceosome dysregulation, leading to mis-splicing of numerous genes that are involved in a variety of retina-specific functions and/or general biological processes, including phototransduction, retinol metabolism, photoreceptor disk morphogenesis, retinal cell polarity, ciliogenesis, cytoskeleton and tight junction organization, waste disposal, inflammation, and apoptosis. Importantly, additional PRPF functions beyond RNA splicing have been documented recently, suggesting a more complex mechanism underlying PRPF-RPs driven disease pathogenesis. The current review focuses on the key RP-PRPF genes, depicting the current understanding of their roles in RNA splicing, impact of their mutations on retinal cell’s transcriptome and phenome, discussed in the context of model species including yeast, zebrafish, and mice. Importantly, information on PRPF functions beyond RNA splicing are discussed, aiming at a holistic investigation of PRPF-RP pathogenesis. Finally, work performed in human patient-specific lab models and developing gene and cell-based replacement therapies for the treatment of PRPF-RPs are thoroughly discussed to allow the reader to get a deeper understanding of the disease mechanisms, which we believe will facilitate the establishment of novel and better therapeutic strategies for PRPF-RP patients. Frontiers Media S.A. 2021-07-28 /pmc/articles/PMC8355544/ /pubmed/34395430 http://dx.doi.org/10.3389/fcell.2021.700276 Text en Copyright © 2021 Yang, Georgiou, Atkinson, Collin, Al-Aama, Nagaraja-Grellscheid, Johnson, Ali, Armstrong, Mozaffari-Jovin and Lako. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Yang, Chunbo Georgiou, Maria Atkinson, Robert Collin, Joseph Al-Aama, Jumana Nagaraja-Grellscheid, Sushma Johnson, Colin Ali, Robin Armstrong, Lyle Mozaffari-Jovin, Sina Lako, Majlinda Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond |
title | Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond |
title_full | Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond |
title_fullStr | Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond |
title_full_unstemmed | Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond |
title_short | Pre-mRNA Processing Factors and Retinitis Pigmentosa: RNA Splicing and Beyond |
title_sort | pre-mrna processing factors and retinitis pigmentosa: rna splicing and beyond |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355544/ https://www.ncbi.nlm.nih.gov/pubmed/34395430 http://dx.doi.org/10.3389/fcell.2021.700276 |
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