Analysis of the biological significance and molecular mechanisms of meiosis-specific production of Mga variants.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16147
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: Saitama Medical University
• Principal Investigator: Uranishi Kousuke 埼玉医科大学, 医学部, 助教 (40783238)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 減数分裂 / PRC1.6 / Mga / Meiosin / Stra8

Outline of Final Research Achievements

Our understanding of the molecular mechanisms that prevent precocious meiotic onset by PRC1.6 is far from complete. Moreover, how germ cells impede the function of PRC1.6 for physiological meiotic onset remains totally obscure. In this research project, I have demonstrated that two distinct DNA binding domains of Mga, a scaffolding component of PRC1.6 enables the complex to repress numerous meiosis-related genes. I have also demonstrated that germ cells produced anomalous MGA that functions against the construction of PRC1.6 as a dominant negative regulator via germ cell-specific alternative splicing for promoting progression of meiosis.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

Mgaの下流標的遺伝子や、MgaによるPRC1.6制御機構が明らかになったことによって、配偶子形成や減数分裂開始における分子メカニズムの解明の大きな一歩となった。また、Mgaは多種多様ながんで変異が報告されており、今回の研究で見つかった知見はMga変異型のがんの病態解明にもポジティブな波及効果をもたらすと考えられる。