biostudies-literatureBlake LAPew Charitable TrustsFoundation for the National Institutes of HealthU.S. Department of Health & Human Services | National Institutes of HealthNIGMS NIH HHS2720https://www.ebi.ac.uk/biostudies/studies/S-EPMC10979015biostudies-literatureUnknown15(1)RNA decay is vital for regulating mRNA abundance and gene expression. Existing technologies lack the spatiotemporal precision or transcript specificity to capture the stochastic and transient decay process. We devise a general strategy to inducibly recruit protein factors to modulate target RNA metabolism. Specifically, we introduce a Rapid Inducible Decay of RNA (RIDR) technology to degrade target mRNAs within minutes. The fast and synchronous induction enables direct visualization of mRNA decay dynamics in cells. Applying RIDR to endogenous ACTB mRNA reveals rapid formation and dissolution of RNA granules in pre-existing P-bodies. Time-resolved RNA distribution measurements demonstrate rapid RNA decay inside P-bodies, which is further supported by knocking down P-body constituent proteins. Light and oxidative stress modulate P-body behavior, potentially reconciling the contradictory literature about P-body function. This study reveals compartmentalized RNA decay kinetics, establishing RIDR as a pivotal tool for exploring the spatiotemporal RNA metabolism in cells.Nature communicationsA rapid inducible RNA decay system reveals fast mRNA decay in P-bodies.PMC10979015R01GM136897R35GM150941R35 GM149329R35 GM150941T32 GM007445R01 GM136897T32 GM00840300030601R35GM149329Inoue TWatkins LLiu YBlake LAWu BfalseA rapid inducible RNA decay system reveals fast mRNA decay in P-bodies.RNA decay is vital for regulating mRNA abundance and gene expression. Existing technologies lack the spatiotemporal precision or transcript specificity to capture the stochastic and transient decay process. We devise a general strategy to inducibly recruit protein factors to modulate target RNA metabolism. Specifically, we introduce a Rapid Inducible Decay of RNA (RIDR) technology to degrade target mRNAs within minutes. The fast and synchronous induction enables direct visualization of mRNA decay dynamics in cells. Applying RIDR to endogenous ACTB mRNA reveals rapid formation and dissolution of RNA granules in pre-existing P-bodies. Time-resolved RNA distribution measurements demonstrate rapid RNA decay inside P-bodies, which is further supported by knocking down P-body constituent proteins. Light and oxidative stress modulate P-body behavior, potentially reconciling the contradictory literature about P-body function. This study reveals compartmentalized RNA decay kinetics, establishing RIDR as a pivotal tool for exploring the spatiotemporal RNA metabolism in cells.2024-01-01T00:00:00Z2024 Mar2025-04-04T20:16:30.14Z2025-04-04T20:16:30.14ZS-EPMC109790153854871810.1038/s41467-024-46943-z