Correlation between mRNA poly(A) tail length and translational activity

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K15719
• 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 University
• Principal Investigator: Ogami Koichi 名古屋大学, 医学系研究科, 助教 (70796523)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 翻訳 / ポリA鎖 / ナノポアシークエンサー / directRNA sequencing / TOP mRNA

Outline of Final Research Achievements

Poly(A) tail length has long been believed to correlate positively with translation efficiency. In fact, multiple studies have reported the correlation in various types of cells. However, the concept is being challenged by recent studies utilizing the next generation sequencing, all agreeing that the correlation was observed only in the early embryonic cells but absent in the later developmental stages. To address the controversy, we employed direct RNA-sequencing in the combination with polysome fraction. We have identified 335 genes in which positive correlation is evident and found that large majority of them consist of ribosome protein genes and mitochondrial function-related genes. We further found that this exceptional correlation can be explained by the presence of 5'TOP or 5'TOP-like sequences at the 5' most end of these genes and that the RNA-binding protein LARP1, which directly binds to 5'TOP sequences, is correlated with the coupling of polyA-tail length and translation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

遺伝子発現の転写後における調節は、しばしばポリA鎖の分解や伸長を介してなされる。それらの分子メカニズムを理解するにあたって、ポリA鎖の長さと翻訳活性との相関関係の有無は最も根幹的な問いであり、慎重な検討が必要である。本研究では、相関関係の存在に否定的な最近の研究結果に概ね一致する見解が得られたが、その一方で、例外的に強い相関性を示す遺伝子群を複数同定することに成功した。本研究の結果、翻訳におけるポリA鎖の役割について、新たな問いを投げかける重要な知見が得られた。