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MTRACE: Modification-enabled Tracking of RNA-associated Cellular Events

ABSTRACT: The life cycle of RNA is orchestrated by molecular events whose dynamic regulation is fundamental to gene expression and cellular function. However, existing methods face limitations in continuously recording these events in living cells. Here we introduce mTRACE (Modification-enabled Tracking of RNA-associated Cellular Events), a molecular recording framework that leverages RNA modification enzymes to capture the history of RNA-associated cellular processes. By systematically screening 34 candidate enzymes, we identified N6-adenosine methyltransferase M.EcoGII as a highly efficient and unbiased modifier. mTRACE exploits M.EcoGII to install natural and non-disruptive RNA modification, writing durable marks on transcripts undergoing specific molecular events in living cells. We demonstrate that mTRACE enables retrospective tracking of RNA-protein interactions, quantification of translational activity and efficiency by coupling M.EcoGII to ribosomal proteins, and spatial recording of RNA residence across multiple subcellular compartments using engineered M.EcoGII variants. mTRACE provides a general framework for dissecting RNA dynamic regulation and supports multi-dimensional recording of RNA-associated cellular events with spatiotemporal resolution.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307458 | GEO | 2026/09/09

REPOSITORIES: GEO

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