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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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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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 / 血液型D抗原 / SRSF / スプライシング / 軟骨再生 / がん抑制 |
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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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| 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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Report
(4 results)
Research Products
(9 results)
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[Journal Article] Pilot study on novel blood containers with alternative plasticizers for red cell concentrate storage.2017
Author(s)
Morishita Y, Nomura Y, Fukui C, Kawakami T, Ikeda T, Mukai T, Yuba T, Inamura KI, Yamaoka H, Miyazaki KI, Okazaki H, Haishima Y
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Journal Title
PLoS One
Volume: 12
Issue: 9
Pages: e0185737-e0185737
DOI
Related Report
Peer Reviewed
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[Journal Article] Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments.2017
Author(s)
Sumiyo Watanabe , Toru Ogasawara, Yoshifuru Tamura, Taku Saito, Toshiyuki Ikeda, Nobuchika Suzuki, Tatsuo Shimosawa, Shigeru Shibata, Ung-il Chung, Masaomi Nangaku, Shunya Uchida
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Journal Title
PLoS One
Volume: 12
Issue: 3
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63.2017
Author(s)
Taniguchi Y, Kawata M, Chang SH, Mori D, Okada K, Kobayashi H, Sugita S, Hosaka Y, Inui H, Taketomi S, Yano F, Ikeda T, Akiyama H, Mills AA, Chung UI, Tanaka S, Kawaguchi H, and Saito T*
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Journal Title
Arthritis Rheumatol.
Volume: 69
Issue: 3
Pages: 598-609
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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