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Biochim Biophys Acta Gene Regul Mech. 2019 Nov 4:194433. doi: 10.1016/j.bbagrm.2019.194433. [Epub ahead of print]

Splicing in the pathogenesis, diagnosis and treatment of ciliopathies.

Author information

1
Faculty of Medicine, University of Southampton, Human Development and Health, United Kingdom of Great Britain and Northern Ireland; University Hospital Southampton NHS Foundation Trust, United Kingdom of Great Britain and Northern Ireland.
2
Faculty of Medicine, University of Southampton, Human Development and Health, United Kingdom of Great Britain and Northern Ireland; University Hospital Southampton NHS Foundation Trust, United Kingdom of Great Britain and Northern Ireland. Electronic address: d.baralle@soton.ac.uk.

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.

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