Transcription-dependent IgH gene instability by RNA interference

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06485
• 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: Kobayashi Maki 京都大学, 医学研究科, 特定准教授 (20400690)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: RNA干渉 / 抗体遺伝子組換え / アンチセンスオリゴ / ゲノム不安定化 / AID

Outline of Final Research Achievements

We have newly discovered that retrotransposon-derived RNA is important as the nuclear environment essential for DNA cleavage. An entirely new method for evaluating the recombination kinetics of an antibody gene was attempted by the RNA-FISH method using a probe for antibody gene noncoding RNA. RNA derived from the Alu sequence is essential for the regulation of nuclear structure, but it is important for the formation of RNA concentrate at the antibody gene recombination site. hnRNP K, which is essential for DNA cleavage, controles the localization of the antibody gene in the transcription-active region in the nucleus. We also newly found that an RNA-binding protein that bind to the repetitive RNA are essential for the DNA cleavage stage of AID-dependent antibody gene recombination.

Free Research Field

細胞分子生物学

Academic Significance and Societal Importance of the Research Achievements

抗体遺伝子noncoding RNAが濃縮体を形成し、DNA切断や修復の場を与える可能性を見出した。これらの独自性の高い発見が、さらに抗体遺伝子が組換え時に特別な核内環境を要求する条件を特定する契機になると期待される。