| 描述信息 |
pulse chase experiment of: Ribosomes dynamically interact with mRNAs, controlling gene expression by balancing protein synthesis and mRNA stability. However, traditional methods lack temporal resolution of these interactions. Here, we introduce Time-resolved Ribosome Density Profiling (TRiP), combining metabolic RNA labeling and polysome sequencing to map ribosome dynamics across mRNA lifespans. TRiP reveals a conserved temporal symmetry: gene-specific ribosome loading and unloading rates are correlated, creating a self-regulatory loop coupling ribosome dynamics to mRNA stability. Mechanistically, mRNA structural features and m6A methylation fine-tune ribosome dynamics, modulating protein output and transcript half-life. In macrophages, this control enables rapid immune responses by upregulating translation efficiency. Importantly, these principles extend to synthetic mRNAs, where optimizing ribosome dynamics enhances protein production. This work establishes ribosome dynamics as a central gene regulatory mechanism, with key implications for immunity, RNA biology, and mRNA therapeutics. |
