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 MartinoEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1912)


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 



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.


  1. 1.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Flynt AS, Lai EC (2008) Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9:831PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Cech TR, Steitz JA (2014) The noncoding RNA revolution–trashing old rules to forge new ones. Cell 157:77–94PubMedCrossRefGoogle Scholar
  4. 4.
    Gurtan AM, Sharp PA (2013) The role of miRNAs in regulating gene expression networks. J Mol Biol 425:3582–3600PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Bartel DP (2018) Metazoan microRNAs. Cell 173:20–51PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123:631–640PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Chandradoss SD, Schirle NT, Szczepaniak M, MacRae IJ, Joo C (2015) A dynamic search process underlies microRNA targeting. Cell 162:96–107PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Klein M, Chandradoss SD, Depken M, Joo C (2017) Why Argonaute is needed to make microRNA target search fast and reliable. In: Seminars in cell & developmental biology, vol. 65. Academic, New York, pp 20–28Google Scholar
  9. 9.
    Chekulaeva M, Filipowicz W (2009) Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 21:452–60PubMedCrossRefGoogle Scholar
  10. 10.
    Jonas S, Izaurralde E (2015) Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 16:421PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Djuranovic S, Nahvi A, Green R (2012) miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. Science 336:237–240PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Liang Y, Ridzon D, Wong L, Chen C (2007) Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8:166PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Franks A, Airoldi E, Slavov N (2017) Post-transcriptional regulation across human tissues. PLoS Comput Biol 13:e1005535PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Ebert MS, Sharp PA (2012) Roles for microRNAs in conferring robustness to biological processes. Cell 149:515–524PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Berezikov E (2011) Evolution of microRNA diversity and regulation in animals. Nat Rev Genet 12:846PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Joshi A, Beck Y, Michoel T (2012) Post-transcriptional regulatory networks play a key role in noise reduction that is conserved from micro-organisms to mammals. FEBS J 279:3501–3512PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Shimoni Y, Friedlander G, Hetzroni G, Niv G, Altuvia S, Biham O, Margalit H (2007) Regulation of gene expression by small non-coding RNAs: a quantitative view. Mol Syst Biol 3:138PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Tsang J, Zhu J, van Oudenaarden A (2007) MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell 26:753–767PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Re A, Corá D, Taverna D, Caselle M (2009) Genome-wide survey of microRNA-transcription factor feed-forward regulatory circuits in human. Mol BioSyst 5:854–867PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Siciliano V, Garzilli I, Fracassi C, Criscuolo S, Ventre S, Di Bernardo D (2013) MiRNAs confer phenotypic robustness to gene networks by suppressing biological noise. Nat Commun 30:2364CrossRefGoogle Scholar
  24. 24.
    Wang S, Raghavachari S (2011) Quantifying negative feedback regulation by micro-RNAs. Phys Biol 8:055002PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Das J, Chakraborty S, Podder S, Ghosh TC (2013) Complex-forming proteins escape the robust regulations of miRNA in human. FEBS Lett 587:2284–2287PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Obermayer B, Levine E (2014) Exploring the miRNA regulatory network using evolutionary correlations. PLoS Comput Biol 10:e1003860PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Schmiedel JM, Klemm SL, Zheng Y, Sahay A, Blüthgen N, Marks DS, van Oudenaarden A (2015) MicroRNA control of protein expression noise. Science 348:128–132PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Guil S, Esteller M (2015) RNA-RNA interactions in gene regulation: the coding and noncoding players. Trends Biochem Sci 40:248–256PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721PubMedCrossRefGoogle Scholar
  31. 31.
    Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J, Califano A (2011) An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell 147:370–381PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Helwak A, Kudla G, Dudnakova T, Tollervey D (2013) Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153:654–665PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Kim D, Sung YM, Park J, Kim S, Kim J, Park J, Ha H, Bae JY, Kim S, Baek D (2016) General rules for functional microRNA targeting. Nat Genet 48:1517PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Breda J, Rzepiela AJ, Gumienny R, van Nimwegen E, Zavolan M (2015) Quantifying the strength of miRNA-target interactions. Methods 85:90–99PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Arvey A, Larsson E, Sander C, Leslie CS, Marks DS (2010) Target mRNA abundance dilutes microRNA and siRNA activity. Mol Syst Biol 6:363PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Levine E, Zhang Z, Kuhlman T, Hwa T (2007) Quantitative characteristics of gene regulation by small RNA. PLoS Biol 5:e229PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Franco-Zorrilla JM, Valli A, Todesco M, Mateos I, Puga MI, Rubio-Somoza I, Leyva A, Weigel D, García JA, Paz-Ares J (2007) Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet 39:1033PubMedCrossRefGoogle Scholar
  38. 38.
    Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146:353–358PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, Lieberman J (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147:344–357PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA, van Oudenaarden A (2011) MicroRNAs can generate thresholds in target gene expression. Nat Genet 43:854PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, Krauthammer M (2011) In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell 147:382–395PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505:344PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Yuan Y, Liu B, Xie P, Zhang MQ, Li Y, Xie Z, Wang X (2015) Model-guided quantitative analysis of microRNA-mediated regulation on competing endogenous RNAs using a synthetic gene circuit. Proc Natl Acad Sci 112:3158–3163PubMedCrossRefGoogle Scholar
  44. 44.
    Bosia C, Sgrò F, Conti L, Baldassi C, Brusa D, Cavallo F, Di Cunto F, Turco E, Pagnani A, Zecchina R (2017) RNAs competing for microRNAs mutually influence their fluctuations in a highly non-linear microRNA-dependent manner in single cells. Genome Biol 18:37PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15:7PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Leung AK, Sharp PA (2010) MicroRNA functions in stress responses. Mol Cell 22:205–215CrossRefGoogle Scholar
  47. 47.
    Alvarez-Garcia I, Miska EA (2005) MicroRNA functions in animal development and human disease. Development 132:4653–4662PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Anastasiadou E, Jacob LS, Slack FJ (2018) Non-coding RNA networks in cancer. Nat Rev Cancer 18:5CrossRefGoogle Scholar
  49. 49.
    Sanchez-Mejias A, Tay Y (2015) Competing endogenous RNA networks: tying the essential knots for cancer biology and therapeutics. J Hematol Oncol 8:30PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Jens M, Rajewsky N (2015) Competition between target sites of regulators shapes post-transcriptional gene regulation. Nat Rev Genet 16:113PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Denzler R, Agarwal V, Stefano J, Bartel DP, Stoffel M (2014) Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol Cell 54:766–776PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Ala U, Karreth FA, Bosia C, Pagnani A, Taulli R, Léopold V, Tay Y, Provero P, Zecchina R, Pandolfi PP (2013) Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments. Proc Natl Acad Sci 110:7154–7159PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Bosson AD, Zamudio JR, Sharp PA (2014) Endogenous miRNA and target concentrations determine susceptibility to potential ceRNA competition. Mol Cell 56:347–359PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Denzler R, McGeary SE, Agarwal V, Bartel DP, Stoffel M (2016) Impact of microRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression. Mol Cell 64:565–579PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Wang X, Li Y, Xu X, Wang YH (2010) Toward a system-level understanding of microRNA pathway via mathematical modeling. Biosystems 100:31–38PubMedCrossRefGoogle Scholar
  56. 56.
    Lai X, Wolkenhauer O, Vera J (2016) Understanding microRNA-mediated gene regulatory networks through mathematical modelling. Nucleic Acids Res 44:6019–6035PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R (2006) Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20:515–524PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Baccarini A, Chauhan H, Gardner TJ, Jayaprakash AD, Sachidanandam R, Brown BD (2011) Kinetic analysis reveals the fate of a microRNA following target regulation in mammalian cells. Curr Biol 21:369–376PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Figliuzzi M, Marinari E, De Martino A (2013) MicroRNAs as a selective channel of communication between competing RNAs: a steady-state theory. Biophys J 104:1203–1213PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Bosia C, Pagnani A, Zecchina R (2013) Modelling competing endogenous RNA networks. PLoS One 8:e66609PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Noorbakhsh J, Lang AH, Mehta P (2013) Intrinsic noise of microRNA-regulated genes and the ceRNA hypothesis. PLoS One 8:e72676PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Alon U (2006) An introduction to systems biology: design principles of biological circuits. CRC Press, Boca RatonGoogle Scholar
  63. 63.
    Martirosyan A, Figliuzzi M, Marinari E, De Martino A (2016) Probing the limits to microRNA-mediated control of gene expression. PLoS Comput Biol 12:e1004715PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Flondor P, Olteanu M, Stefan R (2018) Qualitative analysis of an ODE model of a class of enzymatic reactions. Bull Math Biol 80:32–45PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Sanchez A, Choubey S, Kondev J (2013) Regulation of noise in gene expression. Annu Rev Biophys 42:469–491PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Van Kampen NG (1992) Stochastic processes in physics and chemistry. Elsevier, AmsterdamGoogle Scholar
  67. 67.
    Swain PS (2004) Efficient attenuation of stochasticity in gene expression through post-transcriptional control. J Mol Biol 344:965–976PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Gillespie DT (1977) Exact stochastic simulation of coupled chemical reactions. J Phys Chem 81:2340–2361CrossRefGoogle Scholar
  69. 69.
    Gibson MA, Bruck J (2000) Efficient exact stochastic simulation of chemical systems with many species and many channels. J Phys Chem A 104:1876–1889CrossRefGoogle Scholar
  70. 70.
    Martirosyan A, Marsili M, De Martino A (2017) Translating ceRNA susceptibilities into correlation functions. Biophys J 113:206–213PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Nitzan M, Steiman-Shimony A, Altuvia Y, Biham O, Margalit H (2014) Interactions between distant ceRNAs in regulatory networks. Biophys J 106:2254–2266PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Osella M, Bosia C, Corá D, Caselle M (2011) The role of incoherent microRNA-mediated feedforward loops in noise buffering. PLoS Comput Biol 7(3):e1001101PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Bosia C, Osella M, El Baroudi M, Corá D, Caselle M (2012) Gene autoregulation via intronic microRNAs and its functions. BMC Syst Biol 6:131PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Riba A, Bosia C, El Baroudi M, Ollino L, Caselle M (2014) A combination of transcriptional and MicroRNA regulation improves the stability of the relative concentrations of target genes. PLoS Comput Biol 10(2):e1003490PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Osella M, Riba A, Testori A, Corá D, Caselle M (2014) Interplay of microRNA and epigenetic regulation in the human regulatory network. Front Genet 5:345PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Grigolon S, Di Patti F, De Martino A, Marinari E (2016) Noise processing by microRNA-mediated circuits: the incoherent feed-forward loop, revisited. Heliyon 2(4):e00095PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Gerstein M, Kundaje A, Hariharan M, Landt S, Yan K et al (2012) Architecture of the human regulatory network derived from ENCODE data. Nature 489:91–100PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Bose I, Ghosh S (2012) Origins of binary gene expression in post-transcriptional regulation by microRNAs. Eur Phys J E 35:102PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Tsimring L (2014) Noise in biology. Rep Prog Phys 77:026601PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Samoilov M, Plyasunov S, Arkin A (2005) Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations. Proc Natl Acad Sci USA 102(7):2310–2315PubMedCrossRefGoogle Scholar
  81. 81.
    Del Giudice M, Bo S, Grigolon S, Bosia C (2018, in press) On the role of microRNA-mediated bimodal gene expression. PLoS Comput BiolGoogle Scholar
  82. 82.
    López-Maury L, Marguerat S, Bähler J (2008) Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation. Nat Rev Genet 9:583PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Mehta P, Goyal S, Wingreen NS (2008) A quantitative comparison of sRNA-based and protein-based gene regulation. Mol Syst Biol 4:221PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Martirosyan A, De Martino A, Pagnani A, Marinari E (2017) ceRNA crosstalk stabilizes protein expression and affects the correlation pattern of interacting proteins. Sci Rep 7:43673Google Scholar
  85. 85.
    Liang H, Li WH (2007) MicroRNA regulation of human protein-protein interaction network. RNA 13:1402–1408PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Yuan X, Liu C, Yang P, He S, Liao Q, Kang S, Zhao Y (2009) Clustered microRNAs’ coordination in regulating protein-protein interaction network. BMC Syst Biol 3:65PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Sass S, Dietmann S, Burk UC, Brabletz S, Lutter D, Kowarsch A, Mayer KF, Brabletz T, Ruepp A, Theis FJ, Wang Y (2011) MicroRNAs coordinately regulate protein complexes. BMC Syst Biol 5:136PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Hsu CW, Juan HF, Huang HC (2008) Characterization of microRNA-regulated protein-protein interaction network. Proteomics 8:1975–1979PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Du B, Wang Z, Zhang X, Feng S, Wang G, He J, Zhang B (2014) MicroRNA-545 suppresses cell proliferation by targeting cyclin D1 and CDK4 in lung cancer cells. PLoS One 9:e88022PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Nadal A, Jares P, Pinyol M, Conde L, Romeu C, Fernández PL, Campo E, Cardesa A (2007) Association of CDK4 and CCND1 mRNA overexpression in laryngeal squamous cell carcinomas occurs without CDK4 amplification. Virchows Arch 450:161–167PubMedCrossRefPubMedCentralGoogle Scholar
  91. 91.
    Kwon J, Lee TS, Lee HW, Kang MC, Yoon HJ, Kim JH, Park JH (2013) Integrin alpha 6: a novel therapeutic target in esophageal squamous cell carcinoma. Int J Oncol 43:1523–1530PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Tkacik G, Callan Jr CG, Bialek W (2008) Information capacity of genetic regulatory elements. Phys Rev E 78:011910CrossRefGoogle Scholar
  93. 93.
    Figliuzzi M, De Martino A, Marinari E (2014) RNA-based regulation: dynamics and response to perturbations of competing RNAs. Biophys J 107:1011–1022PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Detwiler PB, Ramanathan S, Sengupta A, Shraiman BI (2000) Engineering aspects of enzymatic signal transduction: photoreceptors in the retina. Biophys J 79:2801–2817PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Legnini I, Morlando M, Mangiavacchi A, Fatica A, Bozzoni I (2014) A feedforward regulatory loop between HuR and the long noncoding RNA linc-MD1 controls early phases of myogenesis. Mol Cell 53:506–514PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Fiorentino J, De Martino A (2017) Independent channels for miRNA biosynthesis ensure efficient static and dynamic control in the regulation of the early stages of myogenesis. J Theor Biol 430:53–63PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Mauri M, Klumpp S (2014) A model for sigma factor competition in bacterial cells. PLoS Comput Biol 10:e1003845PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Brewster RC, Weinert FM, Garcia HG, Song D, Rydenfelt M, Phillips R (2014) The transcription factor titration effect dictates level of gene expression. Cell 156:1312–1323PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Raveh A, Margaliot M, Sontag ED, Tuller T (2016) A model for competition for ribosomes in the cell. J R Soc Interface 13:20151062PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Loinger A, Shemla Y, Simon I, Margalit H, Biham O (2012) Competition between small RNAs: a quantitative view. Biophys J 102:1712–1721PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Koller E, Propp S, Murray H, Lima W, Bhat B, Prakash TP, Allerson CR, Swayze EE, Marcusson EG, Dean NM (2006) Competition for RISC binding predicts in vitro potency of siRNA. Nucleic Acids Res 34:4467–4476PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Pitchiaya S, Heinicke LA, Park JI, Cameron EL, Walter NG (2017) Resolving subcellular miRNA trafficking and turnover at single-molecule resolution. Cell Rep 19:630–642PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Levine E, McHale P, Levine H (2007) Small regulatory RNAs may sharpen spatial expression patterns. PLoS Comput Biol 3:e233PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Teimouri H, Korkmazhan E, Stavans J, Levine E (2017) Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria. Phys Biol 14:056001PubMedCrossRefPubMedCentralGoogle Scholar

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
    Email author
  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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