Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

Modelling Competing Endogenous RNA Networks

1 , * , 1 , 2 , 1 , 2

PLoS ONE

Public Library of Science

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      MicroRNAs (miRNAs) are small RNA molecules, about 22 nucleotide long, which post-transcriptionally regulate their target messenger RNAs (mRNAs). They accomplish key roles in gene regulatory networks, ranging from signaling pathways to tissue morphogenesis, and their aberrant behavior is often associated with the development of various diseases. Recently it has been experimentally shown that the way miRNAs interact with their targets can be described in terms of a titration mechanism. From a theoretical point of view titration mechanisms are characterized by threshold effect at near-equimolarity of the different chemical species, hypersensitivity of the system around the threshold, and cross-talk among targets. The latter characteristic has been lately identified as competing endogenous RNA (ceRNA) effect to mark those indirect interactions among targets of a common pool of miRNAs they are in competition for. Here we propose a stochastic model to analyze the equilibrium and out-of-equilibrium properties of a network of miRNAs interacting with mRNA targets. In particular we are able to describe in detail the peculiar equilibrium and non-equilibrium phenomena that the system displays in proximity to the threshold: (i) maximal cross-talk and correlation between targets, (ii) robustness of ceRNA effect with respect to the model's parameters and in particular to the catalyticity of the miRNA-mRNA interaction, and (iii) anomalous response-time to external perturbations.

      Related collections

      Most cited references 33

      • Record: found
      • Abstract: found
      • Article: not found

      A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

      Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Nature, nurture, or chance: stochastic gene expression and its consequences.

        Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.
          Bookmark
          • Record: found
          • Abstract: found
          • Article: not found

          Stochasticity in gene expression: from theories to phenotypes.

          Genetically identical cells exposed to the same environmental conditions can show significant variation in molecular content and marked differences in phenotypic characteristics. This variability is linked to stochasticity in gene expression, which is generally viewed as having detrimental effects on cellular function with potential implications for disease. However, stochasticity in gene expression can also be advantageous. It can provide the flexibility needed by cells to adapt to fluctuating environments or respond to sudden stresses, and a mechanism by which population heterogeneity can be established during cellular differentiation and development.
            Bookmark

            Author and article information

            Affiliations
            [1 ]Human Genetics Foundation (HuGeF), Torino, Italy
            [2 ]Physics Department and Center for Computational Sciences, Politecnico Torino, Torino, Italy
            Memorial Sloan Kettering Cancer Center, United States of America
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            Conceived and designed the experiments: CB AP RZ. Performed the experiments: CB AP. Analyzed the data: CB AP. Wrote the paper: CB AP RZ.

            Contributors
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, USA )
            1932-6203
            2013
            26 June 2013
            : 8
            : 6
            23840508
            3694070
            PONE-D-13-01298
            10.1371/journal.pone.0066609
            (Editor)

            This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

            Counts
            Pages: 13
            Funding
            RZ acknowledges support from the European Research Council Grant No. OPTINF 267915. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
            Categories
            Research Article
            Biology
            Biochemistry
            Nucleic Acids
            RNA
            RNA processing
            Biophysics
            Nucleic Acids
            RNA
            RNA processing
            Computational Biology
            Genetics
            Gene Expression
            RNA processing
            Molecular Cell Biology
            Gene Expression
            RNA processing
            Nucleic Acids
            RNA
            RNA processing
            Mathematics
            Applied Mathematics
            Probability Theory
            Stochastic Processes
            Physics
            Biophysics
            Nucleic Acids
            RNA
            RNA processing

            Uncategorized

            Comments

            Comment on this article