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Kinetic Modelling of Competition and Depletion of Shared miRNAs by Competing Endogenous RNAs

  • Araks Martirosyan
  • Marco Del Giudice
  • Chiara Enrico Bena
  • Andrea Pagnani
  • Carla Bosia
  • Andrea De Martino
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1912)

Abstract

Non-coding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA–RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting, e.g., the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell’s proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.

Key words

miRNA ceRNA Competition Sponging Mathematical modeling 

Notes

Acknowledgements

Work supported by the European Union’s Horizon 2020 research and innovation programme MSCA-RISE-2016 under grant agreement No 734439 INFERNET. We are indebted with Matteo Figliuzzi, Enzo Marinari, Matteo Marsili and Riccardo Zecchina for our fruitful and enjoyable collaboration.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Araks Martirosyan
    • 1
    • 2
  • Marco Del Giudice
    • 3
    • 4
  • Chiara Enrico Bena
    • 3
    • 4
  • Andrea Pagnani
    • 3
    • 4
  • Carla Bosia
    • 3
    • 4
  • Andrea De Martino
    • 5
    • 6
  1. 1.Laboratory of Glia BiologyVIB-KU Leuven Center for Brain and Disease ResearchLeuvenBelgium
  2. 2.KU Leuven, Department of NeuroscienceLeuvenBelgium
  3. 3.DISATPolitecnico di TorinoTurinItaly
  4. 4.Italian Institute for Genomic MedicineTurinItaly
  5. 5.Soft & Living Matter LabCNR-NANOTECRomeItaly
  6. 6.Italian Institute for Genomic MedicineTurinItaly

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