A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.

It is well known that, under suitable conditions, microRNAs are able to fine tune the relative concentration of their targets to any desired value. We show that this function is particularly effective when one of the targets is a Transcription Factor (TF) which regulates the other targets. This comb...

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Autores principales:	Andrea Riba, Carla Bosia, Mariama El Baroudi, Laura Ollino, Michele Caselle
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c4d9535c59ab42b895610361c47a6295
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spelling	oai:doaj.org-article:c4d9535c59ab42b895610361c47a62952021-11-18T05:53:07ZA combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.1553-734X1553-735810.1371/journal.pcbi.1003490https://doaj.org/article/c4d9535c59ab42b895610361c47a62952014-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586138/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358It is well known that, under suitable conditions, microRNAs are able to fine tune the relative concentration of their targets to any desired value. We show that this function is particularly effective when one of the targets is a Transcription Factor (TF) which regulates the other targets. This combination defines a new class of feed-forward loops (FFLs) in which the microRNA plays the role of master regulator. Using both deterministic and stochastic equations, we show that these FFLs are indeed able not only to fine-tune the TF/target ratio to any desired value as a function of the miRNA concentration but also, thanks to the peculiar topology of the circuit, to ensure the stability of this ratio against stochastic fluctuations. These two effects are due to the interplay between the direct transcriptional regulation and the indirect TF/Target interaction due to competition of TF and target for miRNA binding (the so called "sponge effect"). We then perform a genome wide search of these FFLs in the human regulatory network and show that they are characterized by a very peculiar enrichment pattern. In particular, they are strongly enriched in all the situations in which the TF and its target have to be precisely kept at the same concentration notwithstanding the environmental noise. As an example we discuss the FFL involving E2F1 as Transcription Factor, RB1 as target and miR-17 family as master regulator. These FFLs ensure a tight control of the E2F/RB ratio which in turns ensures the stability of the transition from the G0/G1 to the S phase in quiescent cells.Andrea RibaCarla BosiaMariama El BaroudiLaura OllinoMichele CasellePublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 2, p e1003490 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Andrea Riba Carla Bosia Mariama El Baroudi Laura Ollino Michele Caselle A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.
description	It is well known that, under suitable conditions, microRNAs are able to fine tune the relative concentration of their targets to any desired value. We show that this function is particularly effective when one of the targets is a Transcription Factor (TF) which regulates the other targets. This combination defines a new class of feed-forward loops (FFLs) in which the microRNA plays the role of master regulator. Using both deterministic and stochastic equations, we show that these FFLs are indeed able not only to fine-tune the TF/target ratio to any desired value as a function of the miRNA concentration but also, thanks to the peculiar topology of the circuit, to ensure the stability of this ratio against stochastic fluctuations. These two effects are due to the interplay between the direct transcriptional regulation and the indirect TF/Target interaction due to competition of TF and target for miRNA binding (the so called "sponge effect"). We then perform a genome wide search of these FFLs in the human regulatory network and show that they are characterized by a very peculiar enrichment pattern. In particular, they are strongly enriched in all the situations in which the TF and its target have to be precisely kept at the same concentration notwithstanding the environmental noise. As an example we discuss the FFL involving E2F1 as Transcription Factor, RB1 as target and miR-17 family as master regulator. These FFLs ensure a tight control of the E2F/RB ratio which in turns ensures the stability of the transition from the G0/G1 to the S phase in quiescent cells.
format	article
author	Andrea Riba Carla Bosia Mariama El Baroudi Laura Ollino Michele Caselle
author_facet	Andrea Riba Carla Bosia Mariama El Baroudi Laura Ollino Michele Caselle
author_sort	Andrea Riba
title	A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.
title_short	A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.
title_full	A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.
title_fullStr	A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.
title_full_unstemmed	A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.
title_sort	combination of transcriptional and microrna regulation improves the stability of the relative concentrations of target genes.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/c4d9535c59ab42b895610361c47a6295
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A combination of transcriptional and microRNA regulation improves the stability of the relative concentrations of target genes.

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