ESR4

Understanding the impact of alternative splicing of ciliary genes on the development and maturation of human photoreceptors


Alternative splicing is a pre-mRNA processing step regulating the selection of specific exons/introns to produce different transcripts from one genomic locus. Retinal tissue has one of the highest levels of alternative splicing, and mutations in splicing factors and dysregulation of splicing is associated with retinal disease. A recent study in mouse has shown that retinal development is characterised by dynamic changes in splicing, with differential splicing events occurring more frequently during early development. In particular the photoreceptors are characterised by a specific splicing program that displays a switch like pattern with high exon inclusion levels in photoreceptors and almost complete exclusion outside the retina. Our pilot studies have shown that PROM1 displays increased exon 4 skipping (54%) and exon 24 inclusion (44.4%) during 12th-18th week of human development, a developmental window characterised by photoreceptor differentiation and maturation. ESR4 will investigate the dynamics of PROM1 alternatively spliced isoforms generation and their impact on photoreceptor differentiation and maturation.

Partner: NewCells Biotech Ltd, Newcastle, United Kingdom

Supervisor: prof dr M. Lako