A comparative analysis across species of maternal mRNA regulation in embryos using QUANTA DOI

Mazal Tawil,

D Alcalay,

Pnina Greenberg

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Abstract The post-transcriptional regulation of mRNAs greatly impacts gene expression dynamics, but the underlying regulatory kinetics and sequence rules how they change between organisms remain elusive. Thousands pre-loaded maternal transcripts are post-transcriptionally regulated within metazoan embryos, making it an ideal system to investigate mRNA regulation. We present QUANTA, a computational strategy distinguish transcriptionally silent genes analyze their QUANTA uses kinetic models compare total polyA+ patterns, dissect quantitative rates polyadenylation degradation. analysis maternally provided in zebrafish, frog, mouse human embryos shows that widespread precedes Degradation proportional developmental pace diverge orthologs. Rates also scale by adjusting zebrafish with external temperature. Finally, we implement massively parallel reporter assay is compatible effects 3’UTR sequences on kinetics. pinpoint potential signals 3’UTRs each organism. These reveal accelerate degradation fast-developing organisms, while slow-developing enhance stability. Our work provides general quantify its sequence-based rules.

Language: Английский

An integrative phenotype-structured partial differential equation model for the population dynamics of epithelial-mesenchymal transition DOI Creative Commons

Jules Guilberteau,

Paras Jain, Mohit Kumar Jolly

et al.

npj Systems Biology and Applications, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 6, 2025

Phenotypic heterogeneity along the epithelial-mesenchymal (E-M) axis contributes to cancer metastasis and drug resistance. Recent experimental efforts have collated detailed time-course data on emergence dynamics of E-M in a cell population. However, it remains unclear how different intra- inter-cellular processes shape heterogeneity. Here, using Cell Population Balance model, we capture density phenotypic resulting from interplay between-(a) intracellular regulatory interaction among biomolecules, (b) division death (c) stochastic cell-state transition. We find that while existence depends regulation, gets enhanced with transitions diminished by growth rate differences. Further, resource competition cells can lead both bi-phasic total population and/or bi-stability composition. Overall, our model highlights complex between cellular shaping dynamic patterns

Language: Английский

Citations

1
A comparative analysis across species of maternal mRNA regulation in embryos using QUANTA DOI

Mazal Tawil,

D Alcalay,

Pnina Greenberg

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Abstract The post-transcriptional regulation of mRNAs greatly impacts gene expression dynamics, but the underlying regulatory kinetics and sequence rules how they change between organisms remain elusive. Thousands pre-loaded maternal transcripts are post-transcriptionally regulated within metazoan embryos, making it an ideal system to investigate mRNA regulation. We present QUANTA, a computational strategy distinguish transcriptionally silent genes analyze their QUANTA uses kinetic models compare total polyA+ patterns, dissect quantitative rates polyadenylation degradation. analysis maternally provided in zebrafish, frog, mouse human embryos shows that widespread precedes Degradation proportional developmental pace diverge orthologs. Rates also scale by adjusting zebrafish with external temperature. Finally, we implement massively parallel reporter assay is compatible effects 3’UTR sequences on kinetics. pinpoint potential signals 3’UTRs each organism. These reveal accelerate degradation fast-developing organisms, while slow-developing enhance stability. Our work provides general quantify its sequence-based rules.

Language: Английский

Citations

0