The role of incoherent microRNA-mediated feedforward loops in noise buffering.

MicroRNAs are endogenous non-coding RNAs which negatively regulate the expression of protein-coding genes in plants and animals. They are known to play an important role in several biological processes and, together with transcription factors, form a complex and highly interconnected regulatory netw...

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Autores principales:	Matteo Osella, Carla Bosia, Davide Corá, Michele Caselle
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1beb1324d8774729b468dfb54ad2b99c
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spelling	oai:doaj.org-article:1beb1324d8774729b468dfb54ad2b99c2021-11-18T05:50:39ZThe role of incoherent microRNA-mediated feedforward loops in noise buffering.1553-734X1553-735810.1371/journal.pcbi.1001101https://doaj.org/article/1beb1324d8774729b468dfb54ad2b99c2011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423718/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358MicroRNAs are endogenous non-coding RNAs which negatively regulate the expression of protein-coding genes in plants and animals. They are known to play an important role in several biological processes and, together with transcription factors, form a complex and highly interconnected regulatory network. Looking at the structure of this network, it is possible to recognize a few overrepresented motifs which are expected to perform important elementary regulatory functions. Among them, a special role is played by the microRNA-mediated feedforward loop in which a master transcription factor regulates a microRNA and, together with it, a set of target genes. In this paper we show analytically and through simulations that the incoherent version of this motif can couple the fine-tuning of a target protein level with an efficient noise control, thus conferring precision and stability to the overall gene expression program, especially in the presence of fluctuations in upstream regulators. Among the other results, a nontrivial prediction of our model is that the optimal attenuation of fluctuations coincides with a modest repression of the target expression. This feature is coherent with the expected fine-tuning function and in agreement with experimental observations of the actual impact of a wide class of microRNAs on the protein output of their targets. Finally, we describe the impact on noise-buffering efficiency of the cross-talk between microRNA targets that can naturally arise if the microRNA-mediated circuit is not considered as isolated, but embedded in a larger network of regulations.Matteo OsellaCarla BosiaDavide CoráMichele CasellePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 3, p e1001101 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Matteo Osella Carla Bosia Davide Corá Michele Caselle The role of incoherent microRNA-mediated feedforward loops in noise buffering.
description	MicroRNAs are endogenous non-coding RNAs which negatively regulate the expression of protein-coding genes in plants and animals. They are known to play an important role in several biological processes and, together with transcription factors, form a complex and highly interconnected regulatory network. Looking at the structure of this network, it is possible to recognize a few overrepresented motifs which are expected to perform important elementary regulatory functions. Among them, a special role is played by the microRNA-mediated feedforward loop in which a master transcription factor regulates a microRNA and, together with it, a set of target genes. In this paper we show analytically and through simulations that the incoherent version of this motif can couple the fine-tuning of a target protein level with an efficient noise control, thus conferring precision and stability to the overall gene expression program, especially in the presence of fluctuations in upstream regulators. Among the other results, a nontrivial prediction of our model is that the optimal attenuation of fluctuations coincides with a modest repression of the target expression. This feature is coherent with the expected fine-tuning function and in agreement with experimental observations of the actual impact of a wide class of microRNAs on the protein output of their targets. Finally, we describe the impact on noise-buffering efficiency of the cross-talk between microRNA targets that can naturally arise if the microRNA-mediated circuit is not considered as isolated, but embedded in a larger network of regulations.
format	article
author	Matteo Osella Carla Bosia Davide Corá Michele Caselle
author_facet	Matteo Osella Carla Bosia Davide Corá Michele Caselle
author_sort	Matteo Osella
title	The role of incoherent microRNA-mediated feedforward loops in noise buffering.
title_short	The role of incoherent microRNA-mediated feedforward loops in noise buffering.
title_full	The role of incoherent microRNA-mediated feedforward loops in noise buffering.
title_fullStr	The role of incoherent microRNA-mediated feedforward loops in noise buffering.
title_full_unstemmed	The role of incoherent microRNA-mediated feedforward loops in noise buffering.
title_sort	role of incoherent microrna-mediated feedforward loops in noise buffering.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1beb1324d8774729b468dfb54ad2b99c
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The role of incoherent microRNA-mediated feedforward loops in noise buffering.

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