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.
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.
Biochim Biophys Acta Gene Regul Mech. 2019 Nov-Dec;1862(11-12):194433. doi: 10.1016/j.bbagrm.2019.194433. Epub 2019 Nov 4.
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.
原发性纤毛是上皮细胞顶表面上的重要信号细胞器，在那里它们协调化学感觉、机械感觉和光感觉。运动纤毛在呼吸道、生殖道、脑室和耳朵中建立流体流动方面发挥着核心作用。影响纤毛结构或功能的遗传缺陷会导致广泛的发育和退行性疾病，称为纤毛病。剪接有助于纤毛病的发病机制、诊断和治疗。组织特异性剪接有助于纤毛病表型的组织特异性表现，例如某些遗传缺陷的视网膜特异性效应，这是由于在高度特化的视网膜纤毛细胞（光感受器细胞）中特异性转录本的表达。纤毛病既可以是由于剪接体蛋白中的遗传变异引起的，也可以是由于影响特定纤毛基因剪接的变异引起的。在这里，我们讨论了使用 RNA 序列分析诊断纤毛病的机会和挑战，以及通过靶向剪接以相对无突变的方式治疗纤毛病的潜力。本文是由 Francisco Baralle、Ravindra Singh 和 Stefan Stamm 编辑的题为“RNA 结构和剪接调控”的特刊的一部分。
