CPEB-mediated post-transcriptional regulation of gene expression

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14630
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Nagoya City University
• Principal Investigator: Ogami Koichi 名古屋市立大学, 医薬学総合研究院(薬学), 助教 (70796523)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: RNA結合タンパク質 / mRNA分解 / 翻訳

Outline of Final Research Achievements

The RNA-binding protein CPEB regulates gene expression both positively and negatively. Currently, c-myc mRNA is the only known target that is promptly degraded by a mechanism involving CPEB. In this study, we identified an RNA code comprising of the consesnsus and non-consesnsus CPE sequences that guides CPEB to degrade c-myc mRNA. We also worked on CPEB's role during DNA damage responses, and found that CPEB and its binding poly(A) polymerase PAPD7 are essential for the increase of RNR2 protein after doxorubicin or UV treatment of U2OS cells. While many of the constitutively expressed mRNAs are deadenylated in response to the DNA damages, poly(A) tails of RNR2 mRNA are elongated. Our results suggesting that CPEB-PAPD7 discriminates RNR2 mRNA from the others to indeuce translation during DNA damage response.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

転写後における遺伝子の発現制御は、mRNAの量や翻訳量を決定する重要な過程である。CPEBは、mRNAの3'末端に付加されるポリA鎖の制御によってmRNAの運命を決定する。CPEBは標的遺伝子ごとにポリA鎖短縮化によるmRNA分解促進と伸長による翻訳活性化を使い分けていると考えられるが、CPEBが標的mRNAのどのような情報を読み取って制御の方向を決定しているかなど、CPEBによる遺伝子発現に関わる分子メカニズムには不明な点が多い。本研究は、CPEBによる多様なmRNA制御に、どのような仕組みが関わるのかを完全に理解するために重要な基盤的な知見を与えるものである。