# The Interplay Between Non-Instantaneous Dynamics of mRNA and Bounded Extrinsic Stochastic Perturbations for a Self-Enhancing Transcription Factor

**Authors:** Lorenzo Cabriel, Giulio Caravagna, Sebastiano de Franciscis, Fabio Anselmi, Alberto D’Onofrio

PMC · DOI: 10.3390/e28020238 · 2026-02-19

## TL;DR

The paper explores how mRNA delays and random perturbations affect the behavior of a self-enhancing transcription factor system.

## Contribution

The study reveals how mRNA dynamics and extrinsic noise influence phase transitions and energy spectrum patterns in gene regulatory motifs.

## Key findings

- Non-instantaneous mRNA dynamics significantly impact phase transitions in the system over long timescales.
- Extrinsic stochastic perturbations are amplified with more complex feedback and translation delays.
- Power-law behavior in energy spectra can arise from the filtering nature of the motif structure.

## Abstract

In this work, we consider a simple bistable motif constituted by a self-enhancing Transcription Factor (TF) and its mRNA with non-instantaneous dynamics. In particular, we mainly numerically investigated the impact of bounded stochastic perturbations of Sine–Wiener type affecting the degradation rate/binding rate constant of the TF on the phase-like transitions of the system. We show that the intrinsic exponential delay in the TF positive feedback, due to the presence of a mRNA with slow dynamics, deeply affects the above-mentioned transitions for long but finite times. We also show that, in the case of more complex delays in the feedback and/or in the translation process, the impact of the extrinsic stochasticity is further amplified. We also briefly investigate the power-law behavior (PLB) of the averaged energy spectrum of the TF by showing that, in some cases, the PLB is simply due to the filtering nature of the motif. A similar analysis can also be applied to biological models having a qualitatively similar structure, such as the well-known Capasso and Paveri–Fontana model of cholera spreading.

## Linked entities

- **Proteins:** SEP2 (K-box region and MADS-box transcription factor family protein)
- **Diseases:** cholera (MONDO:0015766)

## Full-text entities

- **Genes:** FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, Bmp2 (bone morphogenetic protein 2) [NCBI Gene 12156] {aka Bmp2a}, Ifit1 (interferon-induced protein with tetratricopeptide repeats 1) [NCBI Gene 15957] {aka GARG-16, IFI-56K, ISG56, Ifi56, P56}, Pou5f1 (POU domain, class 5, transcription factor 1) [NCBI Gene 18999] {aka NF-A3, Oct-3, Oct-3/4, Oct-4, Oct3, Oct3/4}, Tbp (TATA box binding protein) [NCBI Gene 21374] {aka GTF2D1, Gtf2d, SCA17, TFIID}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Lgals3 (lectin, galactose binding, soluble 3) [NCBI Gene 16854] {aka GBP, L-34, Mac-2, gal3}, Itpr3 (inositol 1,4,5-triphosphate receptor 3) [NCBI Gene 16440] {aka IP3R 3, IP3R-3, Ip3r3, Itpr-3, tf}, Ado (2-aminoethanethiol dioxygenase) [NCBI Gene 211488] {aka Gm237}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}
- **Diseases:** injury to (MESH:D014947), tumor (MESH:D009369), cholera (MESH:D002771), infectious diseases (MESH:D003141)
- **Chemicals:** lactose (MESH:D007785), galactose (MESH:D005690), ReLU (-), phorbol ester (MESH:D010703)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Bacillus subtilis (species) [taxon 1423], Mus musculus (house mouse, species) [taxon 10090], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606], Bacteriophage sp. (species) [taxon 38018]
- **Cell lines:** C2C12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0188)

## Figures

16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939622/full.md

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Source: https://tomesphere.com/paper/PMC12939622