Abstract
Changes in transcription factor levels, epigenetic status, splicing kinetics and mRNA degradation can each contribute to changes in the mRNA dynamics of a gene. We present a novel method to identify which of these processes is changed in cells in response to external signals or as a result of a diseased state. The method employs a mathematical model, for which the kinetics of gene regulation, splicing, elongation and mRNA degradation were estimated from experimental data of transcriptional dynamics. The time-dependent dynamics of several species of adipose differentiation-related protein (ADRP) mRNA were measured in response to ligand activation of the transcription factor peroxisome proliferator-activated receptor d (PPARd). We validated the method by monitoring the mRNA dynamics upon gene activation in the presence of a splicing inhibitor. Our mathematical model correctly identifies splicing as the inhibitor target, despite the noise in the data.
| Original language | English |
|---|---|
| Pages (from-to) | 153-161 |
| Journal | Nucleic acids research |
| Volume | 43 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2015 |
Keywords
- differentiation-related protein
- gene-expression
- parameter-estimation
- rna degradation
- adrp expression
- receptor
- cells
- elongation
- promoter
- networks