Transcriptome analyses to investigate the pathogenesis of RNA splicing factor retinitis pigmentosa

Abstract

RNA-splicing factor retinitis pigmentosa (RP) is caused by mutations in components of the spliceosome. RP is an inherited blinding disorder characterized by late-onset retinal degeneration. Currently, mutations in five genes that encode components of the spliceosome have been identified to cause autosomal dominant RP. These are the pre-mRNA processing factors 3, 8, and 31 (PRPF3, 8, and 31), RP9, and SNRNP200. It is unknown how mutations in these ubiquitously expressed genes lead to retina-specific disease. It is hypothesized that mutations in these genes lead to aberrant splicing of pre-mRNA, which in turn causes retinal degeneration. To fully investigate this hypothesis requires the ability to accurately interrogate the transcriptomes of the affected tissue. The recent development of next-generation sequencing-based RNA sequencing (RNA-seq) makes these types of studies possible. This chapter will focus on the RNA splicing factor forms of RP and the application of RNA-seq to study the pathogenesis of these diseases. © 2012 Springer Science+Business Media, LLC.