Identification of mutated splicing factor target genes
Project/Area Number |
26640075
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
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Research Institution | National Hospital Organization Nagoya Medical Center (2015) Kyoto University (2014) |
Principal Investigator |
SANADA MASASHI 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, その他 (20529044)
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 骨髄異形成症候群 / MDS / RNAスプライシング / RNAシーケンス |
Outline of Final Research Achievements |
Although splicing factor mutations are the most important genetic alterations in MDS, little is known about exact gene targets whose abnormal splicing is responsible for the pathogenesis of MDS. SF3B1 and SRSF2 mutations were associated with distinct clinical phenotypes and outcomes together with RNA splicing. To explore the molecular basis of these distinct features in terms of splicing alterations, RNA sequencing data from SF3B1-mutated and SRSF2-mutated bone marrow hematopoietic cells were compared with those without known splicing factor mutations to detect splicing events significantly enriched in splicing factor mutated cases. SF3B1 mutations caused misrecognition of 3’ splice sites of several genes, which included one of the causative genes for congenital sideroblastic anemia. On the other hand, SRSF2 mutations were characterized by modest but more widespread alterations in exon usage of genes. Our results provide insights into the pathogenesis of splicing factor mutated MDS.
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Report
(3 results)
Research Products
(8 results)
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[Journal Article] Aberrant splicing of U12-type introns is the hallmark of ZRSR2 mutant myelodysplastic syndrome.2015
Author(s)
Madan V, Kanojia D, Li J, Okamoto R, Sato-Otsubo A, Kohlmann A, Sanada M, Grossmann V, Sundaresan J, Shiraishi Y, Satoru M, Thol F, Ganser A, Yang H, Haferlach T, Ogawa S, Koeffler HP
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Journal Title
Nature Commun.
Volume: 6
Issue: 1
Pages: 6042-6042
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.2014
Author(s)
7.Sato Y, Maekawa S, Ishii R, Sanada M, Morikawa T, Shiraishi Y, Yoshida K, Nagata Y, Sato-Otsubo A, Yoshizato T, Suzuki H, Shiozawa Y, Kataoka K, Kon A, Aoki K, Chiba K, Tanaka H, Kume H, Miyano S, Fukayama M, Nureki O, Homma Y, Ogawa S.
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Journal Title
Science
Volume: 344
Issue: 6186
Pages: 917-920
DOI
Related Report
Peer Reviewed
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[Presentation] Comprehensive Analysis of Alternative RNA Splicing in Myelodysplastic Syndrome2014
Author(s)
Yusuke Shiozawa, Sato Sato-Otsubo, Anna Gallì, Kenichi Yoshida, Tetsuichi Yoshizato, Yusuke Sato, Keisuke Kataoka,Masashi Sanada,Yuichi Shiraishi, Kenichi Chiba, Satoru Miyano, Luca Malcovati, Mario Cazzola, and Seishi Ogawa
Organizer
55th American Society of Hematology 2014 Annual Meeting
Place of Presentation
San Francisco, USA
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] ZRSR2 Mutations Cause Dysregulated RNA Splicing in MDS2014
Author(s)
Vikas Madan, Deepika Kanojia, Li Jia, Ryoko Okamoto, Aiko Sato-Otsubo, Alexander Kohlmann, Masashi Sanada, Vera Grossmann, Janani Sundaresan, Yuichi Shiraishi, Satoru Miyano, Felicitas Thol, Arnold Ganser, Henry Yang, Torsten Haferlach, Seishi Ogawa, and H. Phillip Koeffler
Organizer
55th American Society of Hematology 2014 Annual Meeting
Place of Presentation
San Francisco, USA
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] SF3B1 PLAYS AN IMPORTANT ROLE IN THE REGULATION OF HEMATOPOIETIC STEMS CELLS, BUT HAPLOINSUFFICIENCY OF SF3B1 MAY NOT BE SOLELY RESPONSIBLE FOR MYELODYSPLASIA2014
Author(s)
Manabu Matsunawa, Ryo Yamamoto, Masashi Sanada, Ayana Kon, Aiko Sato-Otsubo, Yusuke Shiozawa, Kenichi Yoshida, Yasunobu Nagata, Tetsuichi Yoshizato, Makoto Otsu, Kyoichi Isono, Haruhiko Koseki, Hiromitsu Nakauchi, Seishi Ogawa
Organizer
The 19th Congress of European Hematology Association
Place of Presentation
Milan, Italy
Year and Date
2014-06-12 – 2014-06-15
Related Report
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