Optogenetic storage and release of protein and mRNA in live cells and animals

Abstract Cells compartmentalize biomolecules in membraneless structures called biomolecular condensates. While their roles in regulating cellular processes are increasingly understood, tools for their synthetic manipulation remain limited. Here, we introduce RELISR (Reversible Light-Induced Store an...

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Main Authors: Chaeyeon Lee, Jeonghye Yu, Jongpil Shin, Jihwan Yu, Yungyeong Heo, Moosung Lee, Daseuli Yu, YongKeun Park, Won Do Heo
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-61322-y
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author Chaeyeon Lee
Jeonghye Yu
Jongpil Shin
Jihwan Yu
Yungyeong Heo
Moosung Lee
Daseuli Yu
YongKeun Park
Won Do Heo
author_facet Chaeyeon Lee
Jeonghye Yu
Jongpil Shin
Jihwan Yu
Yungyeong Heo
Moosung Lee
Daseuli Yu
YongKeun Park
Won Do Heo
author_sort Chaeyeon Lee
collection DOAJ
description Abstract Cells compartmentalize biomolecules in membraneless structures called biomolecular condensates. While their roles in regulating cellular processes are increasingly understood, tools for their synthetic manipulation remain limited. Here, we introduce RELISR (Reversible Light-Induced Store and Release), an optogenetic condensate system that enables reversible storage and release of proteins or mRNAs. RELISR integrates multivalent scaffolds, optogenetic switches, and cargo-binding domains to trap cargo in the dark and release it upon blue-light exposure. We demonstrate its utility in primary neurons and show that light-triggered release of signaling proteins can modulate fibroblast morphology. Furthermore, light-induced release of cargo mRNA results in protein translation both in vitro and in live mice. RELISR thus provides a versatile platform for spatiotemporal control of protein activity and mRNA translation in complex biological systems, with broad potential for research and therapeutic applications.
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institution Kabale University
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spelling doaj-art-82b5b375ceb54d5181cdf857b8a1d4432025-08-20T04:03:01ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-61322-yOptogenetic storage and release of protein and mRNA in live cells and animalsChaeyeon Lee0Jeonghye Yu1Jongpil Shin2Jihwan Yu3Yungyeong Heo4Moosung Lee5Daseuli Yu6YongKeun Park7Won Do Heo8Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Department of Physics, Korea Advanced Institute of Science and Technology (KAIST)Life Science Research Institute, KAISTDepartment of Physics, Korea Advanced Institute of Science and Technology (KAIST)Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)Abstract Cells compartmentalize biomolecules in membraneless structures called biomolecular condensates. While their roles in regulating cellular processes are increasingly understood, tools for their synthetic manipulation remain limited. Here, we introduce RELISR (Reversible Light-Induced Store and Release), an optogenetic condensate system that enables reversible storage and release of proteins or mRNAs. RELISR integrates multivalent scaffolds, optogenetic switches, and cargo-binding domains to trap cargo in the dark and release it upon blue-light exposure. We demonstrate its utility in primary neurons and show that light-triggered release of signaling proteins can modulate fibroblast morphology. Furthermore, light-induced release of cargo mRNA results in protein translation both in vitro and in live mice. RELISR thus provides a versatile platform for spatiotemporal control of protein activity and mRNA translation in complex biological systems, with broad potential for research and therapeutic applications.https://doi.org/10.1038/s41467-025-61322-y
spellingShingle Chaeyeon Lee
Jeonghye Yu
Jongpil Shin
Jihwan Yu
Yungyeong Heo
Moosung Lee
Daseuli Yu
YongKeun Park
Won Do Heo
Optogenetic storage and release of protein and mRNA in live cells and animals
Nature Communications
title Optogenetic storage and release of protein and mRNA in live cells and animals
title_full Optogenetic storage and release of protein and mRNA in live cells and animals
title_fullStr Optogenetic storage and release of protein and mRNA in live cells and animals
title_full_unstemmed Optogenetic storage and release of protein and mRNA in live cells and animals
title_short Optogenetic storage and release of protein and mRNA in live cells and animals
title_sort optogenetic storage and release of protein and mrna in live cells and animals
url https://doi.org/10.1038/s41467-025-61322-y
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