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<p>Artificial biomolecular condensates have emerged as powerful tools for controlling cellular behaviour. Here we introduce a method to build artificial condensates within living mammalian cells by designing modular RNA motifs composed of a single short RNA strand. These condensates emerge spontaneously, creating RNA-rich compartments that remain separated from their surrounding environment. The RNA sequences include stem–loop domains that fold as the RNA is transcribed, and then condense in the nucleus and cytoplasm through loop–loop interactions. These sequences can be optimized and diversified, enabling the generation of distinct, non-mixing condensate populations and the programmable control of their subcellular localization. The RNA motifs can also be modified to recruit small molecules, proteins and RNA molecules in a sequence-specific manner to the RNA-rich phase. By introducing RNA linkers, we can build condensates with multiple subcompartments, whose organization can be controlled by tuning the linker stoichiometry. These artificial condensates provide a versatile platform for studying and manipulating molecular functions inside living cells.</p>

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Programmable artificial RNA condensates in mammalian cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月29日

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  • Shiyi Li,
  • Yuna Kim,
  • Kevin Wang,
  • Eric John Payson,
  • Anli A. Tang,
  • Maria Villalba Nieto,
  • Dino Osmanovic,
  • Madison Yang,
  • Diego Dilao,
  • Alexandra Bermudez,
  • Wen Xiao,
  • Melody M. H. Li,
  • Neil Y. C. Lin,
  • Kathrin Plath,
  • Douglas L. Black,
  • Elisa Franco

摘要

Artificial biomolecular condensates have emerged as powerful tools for controlling cellular behaviour. Here we introduce a method to build artificial condensates within living mammalian cells by designing modular RNA motifs composed of a single short RNA strand. These condensates emerge spontaneously, creating RNA-rich compartments that remain separated from their surrounding environment. The RNA sequences include stem–loop domains that fold as the RNA is transcribed, and then condense in the nucleus and cytoplasm through loop–loop interactions. These sequences can be optimized and diversified, enabling the generation of distinct, non-mixing condensate populations and the programmable control of their subcellular localization. The RNA motifs can also be modified to recruit small molecules, proteins and RNA molecules in a sequence-specific manner to the RNA-rich phase. By introducing RNA linkers, we can build condensates with multiple subcompartments, whose organization can be controlled by tuning the linker stoichiometry. These artificial condensates provide a versatile platform for studying and manipulating molecular functions inside living cells.