Splicing in the pathogenesis, diagnosis and treatment of ciliopathies
Splicing in the pathogenesis, diagnosis and treatment of ciliopathies
Primary cilia are essential signalling organelles found on the apical surface of epithelial cells, where they coordinate chemosensation, mechanosensation and light sensation. Motile cilia play a central role in establishing fluid flow in the respiratory tract, reproductive tract, brain ventricles and ear. Genetic defects affecting the structure or function of cilia can lead to a broad range of developmental and degenerative diseases known as ciliopathies.
Splicing contributes to the pathogenesis, diagnosis and treatment of ciliopathies. Tissue-specific alternative splicing contributes to the tissue-specific manifestation of ciliopathy phenotypes, for example the retinal-specific effects of some genetic defects, due to specific transcript expression in the highly specialised ciliated cells of the retina, the photoreceptor cells. Ciliopathies can arise both as a result of genetic variants in spliceosomal proteins, or as a result of variants affecting splicing of specific cilia genes. Here we discuss the opportunities and challenges in diagnosing ciliopathies using RNA sequence analysis and the potential for treating ciliopathies in a relatively mutation-neutral way by targeting splicing. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.
1-29
Wheway, Gabrielle
2e547e5d-b921-4243-a071-2208fd4cc090
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
November 2019
Wheway, Gabrielle
2e547e5d-b921-4243-a071-2208fd4cc090
Lord, Jenny
e1909780-36cd-4705-b21e-4580038d4ec6
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Wheway, Gabrielle, Lord, Jenny and Baralle, Diana
(2019)
Splicing in the pathogenesis, diagnosis and treatment of ciliopathies.
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1862 (11-12), , [194433].
(doi:10.1016/j.bbagrm.2019.194433).
Abstract
Primary cilia are essential signalling organelles found on the apical surface of epithelial cells, where they coordinate chemosensation, mechanosensation and light sensation. Motile cilia play a central role in establishing fluid flow in the respiratory tract, reproductive tract, brain ventricles and ear. Genetic defects affecting the structure or function of cilia can lead to a broad range of developmental and degenerative diseases known as ciliopathies.
Splicing contributes to the pathogenesis, diagnosis and treatment of ciliopathies. Tissue-specific alternative splicing contributes to the tissue-specific manifestation of ciliopathy phenotypes, for example the retinal-specific effects of some genetic defects, due to specific transcript expression in the highly specialised ciliated cells of the retina, the photoreceptor cells. Ciliopathies can arise both as a result of genetic variants in spliceosomal proteins, or as a result of variants affecting splicing of specific cilia genes. Here we discuss the opportunities and challenges in diagnosing ciliopathies using RNA sequence analysis and the potential for treating ciliopathies in a relatively mutation-neutral way by targeting splicing. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.
Text
PCD.BBA.BBAGRM_2019_88_Revision 1_V0
- Accepted Manuscript
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Accepted/In Press date: 17 September 2019
e-pub ahead of print date: 4 November 2019
Published date: November 2019
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Local EPrints ID: 436723
URI: http://eprints.soton.ac.uk/id/eprint/436723
ISSN: 1874-9399
PURE UUID: c37efcce-8e3f-4f54-88ee-081d37da264d
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Date deposited: 03 Jan 2020 11:03
Last modified: 17 Mar 2024 03:13
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Author:
Jenny Lord
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