2003 Fiscal Year Final Research Report Summary
Function of PAP-1,a causative gene for retinitis pigmentosa
| Project/Area Number |
14370551
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
ARIGA Sanae Hokkaido Univ., Grad School of Aggr., Prof., 大学院・農学研究科, 教授 (90184283)
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| Co-Investigator(Kenkyū-buntansha) |
TAIRA Takahiro Hokkaido Univ., Grad School of Pharm.Sci., Asso.Prof., 大学院・薬学研究科, 助教授 (70197036)
ARIGA Hiroyoshi Hokkaido Univ., Grad School of Pharm.Sci., Prof., 大学院・薬学研究科, 教授 (20143505)
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| Project Period (FY) |
2002 – 2003
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| Keywords | PAP-1 / c-Myc / RP9 / retinitis pigmentosa / splicing / Pim-1 / phosphorylation / retina |
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| Research Abstract |
PAP-1, a phosphorylation target of the Pim1 oncogene, has recently been implicated as the defective gene in RP9, one type of autosomal dominant retinitis pigmentosa (adRP). However, RP9 is a rare disease and only two missense mutations have been described, so the report of a link between PAP-1 and RP9 was tentative. The precise cellular role of PAP-1 was also unknown at that time. We now report that PAP-1 localizes in nuclear speckles containing the splicing factor SC35 and interacts directly with another splicing factor, U2AF35. Furthermore we used an in vivo splicing assay to show that PAP-1 has an activity which alters the pattern of pre-mRNA splicing and that this activity is dependent on the phosphorylation state of PAP-1. We used the same splicing assay to examine the activities of two mutant forms of PAP-1 found in RP9 patients. The results showed that while one of the mutations, H137L, had no effect on splicing activity compared with that of wild-type PAP-1, the other, D170G, resulted in both a defect in splicing activity and a decreased proportion of phosphorylated PAP-1. The D17OG mutation may therefore cause RP by altering splicing of retinal genes through a decrease in PAP-1 phosphorylation These results demonstrate that PAP-1 has a role in pre-mRNA splicing and, given that three other splicing factors have been implicated in adRP, this finding provides compelling further evidence that PAP-1 is indeed the RP9 gene.
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Research Products
(13 results)
