ArticleProceedings of the National Academy of Sciences of the United States of America2015
Genome-wide modeling of transcription kinetics reveals patterns of RNA production delays.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
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- Combined modelling of mRNA decay dynamics and single-molecule imaging in the Drosophila embryo uncovers a role for P-bodies in 5' to 3' degradation.PLoS biology · 2023Article
- Landscape Zooming toward the Prediction of RNA Cotranscriptional Folding.Journal of chemical theory and computation · 2022Article
- Inferring kinetic parameters of oscillatory gene regulation from single cell time-series data.Journal of the Royal Society, Interface · 2021Article
- Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation.Nucleic acids research · 2020Article
- Combinatorial dynamics of protein synthesis time delay and negative feedback loop in NF-IET systems biology · 2020Article
- Cell type specific gene expression profiling reveals a role for complement component C3 in neutrophil responses to tissue damage.Scientific reports · 2020Article
- Enhancer RNAs Mediate Estrogen-Induced Decommissioning of Selective Enhancers by Recruiting ERα and Its Cofactor.Cell reports · 2020Article
- Nutrient dose-responsive transcriptome changes driven by Michaelis-Menten kinetics underlie plant growth rates.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Stochastic simulation and statistical inference platform for visualization and estimation of transcriptional kinetics.PloS one · 2020Article
- Long-Chain Non-Coding SOX21-AS1 Promotes Proliferation and Migration of Breast Cancer Cells Through the PI3K/AKT Signaling Pathway.Cancer management and research · 2020Article
- RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicing.Genome research · 2019Article
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
Abstract
Genes with similar transcriptional activation kinetics can display very different temporal mRNA profiles because of differences in transcription time, degradation rate, and RNA-processing kinetics. Recent studies have shown that a splicing-associated RNA production delay can be significant. To investigate this issue more generally, it is useful to develop methods applicable to genome-wide datasets. We introduce a joint model of transcriptional activation and mRNA accumulation that can be used for inference of transcription rate, RNA production delay, and degradation rate given data from high-throughput sequencing time course experiments. We combine a mechanistic differential equation model with a nonparametric statistical modeling approach allowing us to capture a broad range of activation kinetics, and we use Bayesian parameter estimation to quantify the uncertainty in estimates of the kinetic parameters. We apply the model to data from estrogen receptor α activation in the MCF-7 breast cancer cell line. We use RNA polymerase II ChIP-Seq time course data to characterize transcriptional activation and mRNA-Seq time course data to quantify mature transcripts. We find that 11% of genes with a good signal in the data display a delay of more than 20 min between completing transcription and mature mRNA production. The genes displaying these long delays are significantly more likely to be short. We also find a statistical association between high delay and late intron retention in pre-mRNA data, indicating significant splicing-associated production delays in many genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.