temporal and tissue specific regulation of rp-associated splicing factor genes prpf3, prpf31 and prpc8—implications in the pathogenesis of rp时间和组织特定的监管rp-associated剪接因子基因prpf3 prpf31和prpc8-implications rp的发病机理.pdf

Temporal and Tissue Specific Regulation of RP- Associated Splicing Factor Genes PRPF3, PRPF31 and PRPC8—Implications in the Pathogenesis of RP 1 1 1 1 1 4 Huibi Cao , Jing Wu , Simon Lam , Rongqi Duan , Catherine Newnham , Robert S. Molday , John J. 5 5 1,2,3 Graziotto , Eric A. Pierce , Jim Hu * 1 Physiology and Experimental Medicine Program, University of Toronto, Toronto, Canada, 2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada, 3 Department of Paediatrics, University of Toronto, Toronto, Canada, 4 Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada, 5 F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America Abstract Background: Genetic mutations in several ubiquitously expressed RNA splicing genes such as PRPF3, PRP31 and PRPC8, have been found to cause retina-specific diseases in humans. To understand this intriguing phenomenon, most studies have been focused on testing two major hypotheses. One hypothesis assumes that these mutations interrupt retina-specific interactions that are important for RNA splicing, implying that there are specific components in the retina interacting with these splicing factors. The second hypothesis suggests that these mutations have only a mild effect on the protein function and thus affect only the metabolically highly active cells such as retinal photoreceptors. Methodology/Principal Findings: We examined the second hypothesis using the PRPF3 gene as an example. We analyzed the spatial and tempo