ole of R-loop in antibody class switching and B cell lymphomagenesis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06015
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Kyoto University
• Principal Investigator: Begum Nasim 京都大学, 医学研究科, 特定准教授 (80362507)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: CSR / AID / HNRNPU / DNA Repair / NHEJ / MED12

Outline of Final Research Achievements

During class switching in mature B cells, maintaining genomic integrity is essential due to DNA breaks and rearrangements in the antibody gene locus. This study reveals that heterogeneous ribonucleoprotein HNRNPU is pivotal in regulating R-loop dynamics and DNA repair, while MED12 controls DNA breakage and locus-specific conformation. HNRNPU interacts with DNA repair factors and binds to the Ig locus's G4 RNA/DNA structures. Loss of HNRNPU disrupts DNA repair, leading to R-loop imbalances and hindering antibody class switch processes. Conversely, MED12 loss inhibits recombination by impairing AID-induced DNA breaks and S-S synapsis, which is crucial for bringing recombining loci into proximity. Thus, HNRNPU and MED12 are critical in coordinating immune responses and maintaining genomic stability.

Free Research Field

Molecular Immunology

Academic Significance and Societal Importance of the Research Achievements

The novel findings regarding the regulatory roles of HNRNPU and MED12 in recombination in B cells offer fresh perspectives on immune system functionality and linked genomic instability. These insights hold promise for the development of innovative diagnostic and therapeutic approaches in the future.