細胞間輸送に特化した円形RNAの研究成果(Paper shows circular RNA is preferentially packaged for transport between cells)

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2025-10-02 デラウェア大学 (UD)

デラウェア大学のモナ・バティッシュ准教授らの研究により、細胞間の情報伝達を担うエクソソーム内では、円形RNA(circular RNA)が優先的に輸送されることが判明した。線状RNAよりも安定で分解されにくい円形RNAは、細胞から放出されるエクソソームに選択的に梱包され、他の細胞に届けられる。この仕組みは疾患時の細胞間通信やがんなどのRNAバイオマーカー探索に重要な手掛かりを与えるとされる。成果はJohns Hopkins大学と南方医科大学との共同研究で、『Journal of Extracellular Vesicles』誌に掲載された。

<関連情報>

RNAカーゴを細胞外小胞に選別するためのパラメータの定義 Defining the Parameters for Sorting of RNA Cargo Into Extracellular Vesicles

Ahmed Abdelgawad, Yiyao Huang, Olesia Gololobova, Yanbao Yu, Kenneth W. Witwer, Vijay Parashar, Mona Batish
The Journal of Extracellular Vesicles  Published: 07 July 2025
DOI:https://doi.org/10.1002/jev2.70113

細胞間輸送に特化した円形RNAの研究成果(Paper shows circular RNA is preferentially packaged for transport between cells)

ABSTRACT

Extracellular vesicles (EVs) are small particles that are released by cells and mediate cell–cell communication by transferring bioactive molecules such as RNA. RNA cargo of EVs, including coding and non-coding RNAs, can change the behaviour of recipient cells, affecting processes including gene expression, proliferation, and Fapoptosis. CircRNAs are stable and resistant to degradation and have been shown to be enriched in EVs. They play key roles in gene regulation and are also emerging as promising biomarkers for disease diagnosis due to their stability and disease-specific expression. Although microRNAs (miRNAs) are the most well studied RNA cargo of EVs, very little is known about the mechanisms of enrichment of circular RNAs (circRNAs) as well as long linear RNAs. Here, we take a comprehensive genome-wide approach to investigate the role of structuredness and shape along with GC%, size, exon count and coding potential, in the sorting and enrichment of circular and long linear RNAs into EVs. We developed a model using these parameters to predict the likelihood of EV packaging of RNA and it was validated by using single molecule RNA imaging of EV bound RNAs. Furthermore, we found that structuredness could explain the relative enrichment of circRNAs over their linear counterparts. These results were validated on existing public databases of circular and linear RNAs in EVs. By identifying and analysing these factors, we aim to better understand the complex mechanisms behind EV-mediated RNA transfer and its impact on cell communication in both health and disease. This mechanistic understanding of RNA enrichment in EVs is crucial for engineering EVs with selective RNA cargo.

細胞遺伝子工学
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