Dhawan2019 - Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network

  public model
Model Identifier
BIOMD0000000841
Short description
This is a delay differential equation model showing how non-coding RNA, acting as microRNA (miRNA) sponges in a conserved RNA-transcription factor feedback motif, can five rise to oscillatory behaviour.
Format
SBML (L2V4)
Related Publication
  • Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network.
  • Dhawan A, Harris AL, Buffa FM, Scott JG
  • Journal of theoretical biology , 11/ 2019 , Volume 481 , pages: 54-60 , PubMed ID: 30385313
  • Department of Oncology, University of Oxford, Oxford, United Kingdom.
  • Oscillations are crucial to the normal function of living organisms, across a wide variety of biological processes. In eukaryotes, oscillatory dynamics are thought to arise from interactions at the protein and RNA levels; however, the role of non-coding RNA in regulating these dynamics remains understudied. In this work, we show how non-coding RNA acting as microRNA (miRNA) sponges in a conserved miRNA - transcription factor feedback motif, can give rise to oscillatory behaviour, and how to test for this experimentally. Control of these non-coding RNA can dynamically create oscillations or stability, and we show how this behaviour predisposes to oscillations in the stochastic limit. These results, supported by emerging evidence for the role of miRNA sponges in development, point towards key roles of different species of miRNA sponges, such as circular RNA, potentially in the maintenance of yet unexplained oscillatory behaviour. These results help to provide a paradigm for understanding functional differences between the many redundant, but distinct RNA species thought to act as miRNA sponges in nature, such as long non-coding RNA, pseudogenes, competing mRNA, circular RNA, and3' UTRs.
Contributors
Johannes Meyer

Metadata information

hasProperty
Mathematical Modelling Ontology MAMO_0000089

Curation status
Curated

Tags
Name Description Size Actions

Model files

Dhawan2019.xml SBML L2V4 Representation of Dhawan2019 - Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network 37.05 KB Preview | Download

Additional files

Dhawan2019.cps COPASI file of Dhawan2019 - Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network 71.78 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Nov 1, 2019 1:24:01 PM
  • Last Modified: Nov 1, 2019 1:24:01 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Nov 1, 2019 1:24:01 PM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000841
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
C

C25966
0.0 item
M

C25966
0.0 item
F

C813
0.0 item
P

C17207
0.0 item
Reactions
Reactions Rate Parameters
() => (M)

() => ([C25966])
compartment*beta_FM/((gamma_FM/delay(P, tau1))^n+1)

compartment*beta_FM/((gamma_FM/delay([C17207], tau1))^n+1)
gamma_FM = 100.0; n = 8.0; tau1 = 0.5; beta_FM = 200.0
(M + C) => ()

([C25966] + [C25966]) => ()
compartment*k_CM*M*C

compartment*k_CM*[C25966]*[C25966]
k_CM = 10.0
(M + F) => ()

([C25966] + [C813]) => ()
compartment*k_MF*M*F

compartment*k_MF*[C25966]*[C813]
k_MF = 0.1
(F) => ()

([C813]) => ()
compartment*delta_F*F

compartment*delta_F*[C813]
delta_F = 0.1
(P) => ()

([C17207]) => ()
compartment*delta_P*P

compartment*delta_P*[C17207]
delta_P = 0.1
(M) => ()

([C25966]) => ()
compartment*delta_M*M

compartment*delta_M*[C25966]
delta_M = 1.0
() => (F)

() => ([C813])
compartment*alpha_F

compartment*alpha_F
alpha_F = 1.0
() => (P)

() => ([C17207])
compartment*k_P*delay(F, tau2)

compartment*k_P*delay([C813], tau2)
tau2 = 0.5; k_P = 10.0
Curator's comment:
(added: 01 Nov 2019, 13:23:52, updated: 01 Nov 2019, 13:23:52)
Reproduced plot of Figure 2A in the original publication. All initial conditions = 0. Model simulated and plot produced using Wolfram Mathematica 11.3.