title: Temporal and tissue specific regulation of RP-associated splicing factor genes PRPF3, PRPF31 and PRPC8--implications in the pathogenesis of RP.
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.
  
  
  RESULTS
  We examined the second hypothesis using the PRPF3 gene as an example. We analyzed the spatial and temporal expression of the PRPF3 gene in mice and found that it is highly expressed in retinal cells relative to other tissues and its expression is developmentally regulated. In addition, we also found that PRP31 and PRPC8 as well as snRNAs are highly expressed in retinal cells.
  
  
  CONCLUSIONS
  Our data suggest that the retina requires a relatively high level of RNA splicing activity for optimal tissue-specific physiological function. Because the RP18 mutation has neither a debilitating nor acute effect on protein function, we suggest that retinal degeneration is the accumulative effect of decades of suboptimal RNA splicing due to the mildly impaired protein.
authors.affiliation: Physiology and Experimental Medicine Program, University of Toronto, Toronto, Canada.
authors.forename: Huibi
authors.initials: H
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Simon
authors.initials: S
authors.lastname: Lam
authors.forename: Rongqi
authors.initials: R
authors.lastname: Duan
authors.forename: Catherine
authors.initials: C
authors.lastname: Newnham
authors.forename: Robert S
authors.initials: RS
authors.lastname: Molday
authors.forename: John J
authors.initials: JJ
authors.lastname: Graziotto
authors.forename: Eric A
authors.initials: EA
authors.lastname: Pierce
authors.forename: Jim
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009154:Mutation; D009928:Organ Specificity; D012326:RNA Splicing / Q000235:genetics* / Q000502:physiology; D000072260:RNA Splicing Factors; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology; D012174:Retinitis Pigmentosa / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics*; D013997:Time Factors
chemical_list: D005136:Eye Proteins; C555603:PRPF31 protein, mouse; C532027:Prpf3 protein, mouse; D000072260:RNA Splicing Factors; D017414:Ribonucleoprotein, U4-U6 Small Nuclear