Defects at the level of the pre-mRNA splicing process represent a major cause of human disease. Approximately 15–50% of all human disease mutations have been shown to alter functioning of basic and auxiliary splicing elements. These elements are required to ensure proper processing of pre-mRNA splicing molecules, with their disruption leading to misprocessing of the pre-mRNA molecule and disease. The splicing process is a complex process, with much still to be uncovered before we are able to accurately predict whether a reported genomic sequence variant (GV) represents a splicing-associated disease mutation or a harmless polymorphism. Furthermore, even when a mutation is correctly identified as affecting the splicing process, there still remains the difficulty of providing an exact evaluation of the potential impact on disease onset, severity and duration. In this review, we provide a brief overview of splicing diagnostic methodologies, from in silico bioinformatics approaches to wet lab in vitro and in vivo systems to evaluate splicing efficiencies. In particular, we provide an overview of how the latest developments in high-throughput sequencing can be applied to the clinic, and are already changing clinical approaches.
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March 2017
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Phase contrast microscopy showing primary human mesangial cells in culture. Quantification of cell area showed that exposure of mesangial cells to the pro-fibrotic growth factor (TGF-β1) induced morphological cell expansion and hypertrophy, which was reversed following the overexpression of miR-378. Interestingly, transfection of a miR-378 inhibitor induced the expansion of mesangial cells, highlighting the regulatory role of miR-378 in mesangial hypertrophy. Please see the article by Wang et al. (pages 411-423).
Review Article|
February 15 2017
RNA splicing in human disease and in the clinic
Diana Baralle;
Diana Baralle
1Human Development and Health, Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K.
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Emanuele Buratti
2International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy
Correspondence: Dr Emanuele Buratti (email [email protected])
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Publisher: Portland Press Ltd
Received:
October 06 2016
Revision Received:
December 06 2016
Accepted:
December 15 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (5): 355–368.
Article history
Received:
October 06 2016
Revision Received:
December 06 2016
Accepted:
December 15 2016
Citation
Diana Baralle, Emanuele Buratti; RNA splicing in human disease and in the clinic. Clin Sci (Lond) 1 March 2017; 131 (5): 355–368. doi: https://doi.org/10.1042/CS20160211
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