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miRNAs confer phenotypic robustness to gene networks by suppressing biological noise

Author

Listed:
  • Velia Siciliano

    (Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy
    Present address: Department of Biological Engineering, Massachusetts Institute of Technology. 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA)

  • Immacolata Garzilli

    (Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy)

  • Chiara Fracassi

    (Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy)

  • Stefania Criscuolo

    (Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy)

  • Simona Ventre

    (Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy)

  • Diego di Bernardo

    (Telethon Institute of Genetics and Medicine (TIGEM), Via P. Castellino 111, 80131 Naples, Italy
    University of Naples FEDERICO II, Via Claudio 21, 80125 Naples, Italy)

Abstract

miRNAs are small non-coding RNAs able to modulate target gene expression. It has been postulated that miRNAs confer robustness to biological processes, but clear experimental evidence is still missing. Here, using a synthetic biological approach, we demonstrate that microRNAs provide phenotypic robustness to transcriptional regulatory networks by buffering fluctuations in protein levels. We construct a network motif in mammalian cells exhibiting a ‘toggle-switch’ phenotype in which two alternative protein expression levels define its ON and OFF states. The motif consists of an inducible transcription factor that self-regulates its own transcription and that of a miRNA against the transcription factor itself. We confirm, using mathematical modelling and experimental approaches, that the microRNA confers robustness to the toggle-switch by enabling the cell to maintain and transmit its state. When absent, a dramatic increase in protein noise level occurs, causing the cell to randomly switch between the two states.

Suggested Citation

  • Velia Siciliano & Immacolata Garzilli & Chiara Fracassi & Stefania Criscuolo & Simona Ventre & Diego di Bernardo, 2013. "miRNAs confer phenotypic robustness to gene networks by suppressing biological noise," Nature Communications, Nature, vol. 4(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3364
    DOI: 10.1038/ncomms3364
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    Cited by:

    1. Ross D. Jones & Yili Qian & Katherine Ilia & Benjamin Wang & Michael T. Laub & Domitilla Del Vecchio & Ron Weiss, 2022. "Robust and tunable signal processing in mammalian cells via engineered covalent modification cycles," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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