Kinetics of mRNA nuclear export regulate innate immune response gene expression.
Diane LefaudeuxSupriya SenKevin JiangAlexander Hoffmannnull nullPublished in: Nature communications (2022)
The abundance and stimulus-responsiveness of mature mRNA is thought to be determined by nuclear synthesis, processing, and cytoplasmic decay. However, the rate and efficiency of moving mRNA to the cytoplasm almost certainly contributes, but has rarely been measured. Here, we investigated mRNA export rates for innate immune genes. We generated high spatio-temporal resolution RNA-seq data from endotoxin-stimulated macrophages and parameterized a mathematical model to infer kinetic parameters with confidence intervals. We find that the effective chromatin-to-cytoplasm export rate is gene-specific, varying 100-fold: for some genes, less than 5% of synthesized transcripts arrive in the cytoplasm as mature mRNAs, while others show high export efficiency. Interestingly, effective export rates do not determine temporal gene responsiveness, but complement the wide range of mRNA decay rates; this ensures similar abundances of short- and long-lived mRNAs, which form successive innate immune response expression waves.
Keyphrases
- innate immune
- genome wide
- immune response
- gene expression
- rna seq
- binding protein
- genome wide identification
- genome wide analysis
- dna methylation
- single cell
- copy number
- poor prognosis
- dna damage
- oxidative stress
- electronic health record
- toll like receptor
- long non coding rna
- atomic force microscopy
- artificial intelligence
- data analysis