| Literature DB >> 25477385 |
Katja N Rybakova1, Aleksandra Tomaszewska2, Simon van Mourik3, Joke Blom4, Hans V Westerhoff5, Carsten Carlberg2, Frank J Bruggeman6.
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 δ (PPARδ). 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.Entities:
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Year: 2014 PMID： 25477385 PMCID： PMC4288170 DOI： 10.1093/nar/gku1272
Source DB: PubMed Journal: Nucleic Acids Res ISSN： 0305-1048 Impact factor: 16.971