Molecular pathogenesis of spliceosome mutations in MDS

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390242
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University (2013-2014); The University of Tokyo (2012)
• Principal Investigator: MASASHI Sanada 京都大学, 医学(系)研究科(研究院), 研究員 (20529044)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 骨髄異形成症候群 / RNAスプライシング / 造血幹細胞

Outline of Final Research Achievements

Frequent mutation in RNA splicing factors is a cardinal feature of myelodysplastic syndromes. To understand their molecular mechanisms, we constructed model mice for these alterations in this study. In Sf3b1 hetero knockout mice and Srsf2 mutant conditional knock-in mice the number of hematopoietic stem cells are lower than those in wild type mice, and these repopulation capacities are also reduced. And RNA sequencing of hematopoietic stem/ progenitor cells from Srsf2 mutated mice showed abnormal exon usages in many genes. Thus, in conclusion, these findings suggest that RNA spliceosome mutations lead to deregulated hematopoietic stem cell functions likely due to abnormal RNA splicing.

Free Research Field

血液腫瘍学・分子遺伝学