Nothing to declare.
Alternative splicing and retinal degeneration
Article first published online: 5 JUN 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 84, Issue 2, pages 142–149, August 2013
How to Cite
Alternative splicing and retinal degeneration., .
- Issue published online: 9 JUL 2013
- Article first published online: 5 JUN 2013
- Accepted manuscript online: 3 MAY 2013 01:07PM EST
- Manuscript Revised: 30 APR 2013
- Manuscript Accepted: 30 APR 2013
- Manuscript Received: 25 MAR 2013
- National Institutes of Health (Medical Scientist Training Program). Grant Numbers: T32GM007309, R01EY009769, P30EY001765)
- Foundation Fighting Blindness
- Research to Prevent Blindness, Inc.
- alternative splicing;
- retinal degeneration;
- retinitis pigmentosa;
- small molecules
Alternative splicing is highly regulated in tissue-specific and development-specific patterns, and it has been estimated that 15% of disease-causing point mutations affect pre-mRNA splicing. In this review, we consider the cis-acting splice site and trans-acting splicing factor mutations that affect pre-mRNA splicing and contribute to retinal degeneration. Numerous splice site mutations have been identified in retinitis pigmentosa (RP) and various cone-rod dystrophies. Mutations in alternatively spliced retina-specific exons of the widely expressed RPGR and COL2A1 genes lead primarily to X-linked RP and ocular variants of Stickler syndrome, respectively. Furthermore, mutations in general pre-mRNA splicing factors, such as PRPF31, PRPF8, and PRPF3, predominantly cause autosomal dominant RP. These findings suggest an important role for pre-mRNA splicing in retinal homeostasis and the pathogenesis of retinal degenerative diseases. The development of novel therapeutic strategies to modulate aberrant splicing, including small molecule-based therapies, has the potential to lead to new treatments for retinal degenerative diseases.