2018 Fiscal Year Final Research Report
Investigation of the regulatory mechanisms of alternative splicing that regulate cartilage development, hematopoietic differentiation and tumor suppression
| Project/Area Number |
16K10887
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Research Collaborator |
MISHIMA Yuko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 選択的スプライシング / 血球分化 / 軟骨分化 / アポトーシス |
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| Outline of Final Research Achievements |
The synonymous c.960 G>A mutation in the exon 7 of the RhD gene caused exon skipping with sequence specific manner. We found this sequence specificity was dependent on its binding ability to SRSF3 (serine arginine rich splicing family 3) that belonged to exonic splicing enhancer (ESE) binding proteins. SRSF1, SRSF11 and TRA2B also induced chondrogenic differentiation into human mesenchymal stem cells. We also found that γ isoform specific alternative splicing switching of the p63 gene was induced after apoptosis stimulation.
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| Free Research Field |
輸血医学、骨軟骨代謝学
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| Academic Significance and Societal Importance of the Research Achievements |
RhD遺伝子がコードするD抗原は溶血性副作用や新生児溶血性疾患の原因となる主要血液型抗原のひとつであり、その抗原性の変化に関わる選択的スプライシングの機序を初めて分子レベルで明らかにした。D抗原は同時に赤血球の分化マーカーでもあり、本研究の知見は血球分化のメカニズム解明の上でも重要と考えられる。ESE結合分子であるSRSFファミリー分子が選択的スプライシングを介して軟骨分化にも関与している可能性を示した。p63の選択的スプライシングの制御がアポトーシス誘導に重要である可能性を示唆するデータを得た。
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