Understanding the biological roles of circular RNAs through the analysis of their translation mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02155
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 38060:Applied molecular and cellular biology-related
• Research Institution: Kyoto University
• Principal Investigator: Takahashi Kazutoshi 京都大学, iPS細胞研究所, 准教授 (80432326)
• Co-Investigator(Kenkyū-buntansha): 岩崎 未央 京都大学, iPS細胞研究所, 講師 (10722811)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 環状RNA

Outline of Final Research Achievements

This study aimed to map circular RNAs (circRNAs) and establish an analysis pipeline to elucidate the translation mechanism of circRNAs and the physiological significance of their translation products, which have been overlooked to date. We identified approximately 6700 circRNAs expressed in human pluripotent stem cell lines. To determine whether these circRNAs are translated, we identified the regions where they are translated in human pluripotent stem cells using a ribosome profiling strategy. We found that approximately 28,000 regions were translated in human pluripotent stem cells, of which approximately 60% were known coding sequences (CDSs), 20% were variants of known CDSs, and the remaining 20% were novel translated regions. As described above, this study succeeded in obtaining baseline data that will serve as a stepping stone for mapping and translational analysis of circRNAs expressed in pluripotent stem cells.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

真核生物における環状RNAはこれまで存在は示されているが、翻訳に関する報告は少ない。多くが環状RNAを癌や疾患などのバイオマーカーまたは機能性RNAとして報告しているのみであった。近年になり、環状RNAが翻訳されていることを報告した論文が出始めている状況である。本研究は多能性幹細胞で発現する環状RNAを網羅的に同定した。さらに多能性幹細胞における翻訳領域を決定した。今後この基盤データを利用することで、既存のプロテオミクスデータは大幅に拡張され、生命現象を理解するうえで必要な新規分子が同定できると期待される。