TITLE: “Determining mRNA nuclear export kinetics reveals a wide range of values associated with innate immune response genes”
ABSTRACT: The abundance and stimulus-responsiveness of mature mRNA is known to be determined by nuclear synthesis and cytoplasmic decay. However, nuclear processing and export events and may also contribute. Here, we investigated the role nuclear export rates in innate immune gene expression. We generated high spatio-temporal resolution RNA-seq data from endotoxin-stimulated macrophages and developed a mathematical modeling workflow to infer kinetic parameters with associated confidence intervals. We found that the effective chromatin-to-cytoplasm transport rate is gene-specific, varying 100-fold; that means that for many genes, less than 10% of synthesized transcripts make it to the cytoplasm as mature mRNAs. Surprisingly, effective export rates do not control temporal responsiveness directly, but instead appear to have coevolved with mRNA decay rates; that ensures similar abundances of short- and long-lived mRNAs, which form successive waves of innate immune response gene expression programs.
