Elucidation of the intermolecular network and splicing mechanism between blood group D antigen and interacting molecules

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16249
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo (2023); Kyorin University (2021-2022)
• Principal Investigator: Mishima Yuko 東京大学, 医学部附属病院, 届出研究員 (90815771)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: RhD / 発現制御メカニズム

Outline of Final Research Achievements

RhD isoform (RhD DEL7, DEL9, DEL79, DEL89, DEL789), 3-9CE hybrid allele, and normal RhCE forced expression models, as well as forced expression protein of RhAD, ankyrin, protein 42, spectrin α, β, and band3, which are expected to interact with RhD were reacted in various combinations and subjected to immunoprecipitation. The band3 was the only molecule that bound to RhD. However, there were no apparent differences in the binding ability among the full-length RhD protein and the other splicing variants. This is consistent with the results showing no difference in the expression levels among the full-length RhD protein and splicing variants that lacking exons 7-9 in various patterns.

Free Research Field

輸血

Academic Significance and Societal Importance of the Research Achievements

遺伝子変異の表現型からRhDとの相互作用が想定されている分子のうち、band3とRhDが直接結合することを実験的に検証した。しかし、band3とRhDのスプライシングバリアントの結合能に差を認めなかった。この結果はRhDのスプライシングバリアントのmRNAレベル、蛋白レベルの発現量に差がないことと一致しており、RhDの発現制御には選択的スプライシングのほか、未知の結合分子を含めたより複雑な分子間ネットワークが関与することが示唆された。