English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Gene transcription is a critical step in gene expression. The currentlyaccepted physical model of transcription predicts the existence of a physicallimit on the maximal rate of transcription, which does not depend on thetranscribed gene. This limit appears as a result of polymerase "traffic jams"forming in the bulk of the 1D DNA chain at high polymerase concentrations.Recent experiments have, for the first time, allowed one to access live geneexpression dynamics in the Drosophila fly embryo in vivo under the conditionsof heavy polymerase load and test the predictions of the model. Our analysis ofthe data shows that the maximal rate of transcription is indeed the same forthe Hunchback, Snail and Knirps gap genes, and modified gene constructs innuclear cycles 13, 14, but the experimentally observed value of the maximaltranscription rate corresponds to only 40 % of the one predicted by this model.We argue that such a decrease must be due to a slower polymerase elongationrate in the vicinity of the promoter region. This effectively shifts thebottleneck of transcription from the bulk to the promoter region of the gene.We suggest a quantitative explanation of the difference by taking into accountabortive transcription initiation. Our calculations based on the independentlymeasured abortive initiation constant in vitro confirm this hypothesis and findquantitative agreement with MS2 fluorescence live imaging data in the earlyfruit fly embryo. If our explanation is correct, then the transcription ratecannot be increased by replacing "slow codons" in the bulk with synonymouscodons, and experimental efforts must be focused on the promoter regioninstead. This study extends our understanding of transcriptional regulation,re-examines physical constraints on the kinetics of transcription andre-evaluates the validity of the standard TASEP model of transcription.

Abortive Initiation as a Bottleneck for Transcription in the Early Drosophila Embryo