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Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs

Analysis of transcription regulatory networks has revealed many principal features that govern gene expression regulation. MicroRNAs (miRNAs) have emerged as another major class of gene regulators that influence gene expression post-transcriptionally, but there remains a need to assess quantitativel...

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Autores principales: Guo, Yu, Alexander, Katherine, Clark, Andrew G., Grimson, Andrew, Yu, Haiyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066619/
https://www.ncbi.nlm.nih.gov/pubmed/27604961
http://dx.doi.org/10.1261/rna.048025.114
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author Guo, Yu
Alexander, Katherine
Clark, Andrew G.
Grimson, Andrew
Yu, Haiyuan
author_facet Guo, Yu
Alexander, Katherine
Clark, Andrew G.
Grimson, Andrew
Yu, Haiyuan
author_sort Guo, Yu
collection PubMed
description Analysis of transcription regulatory networks has revealed many principal features that govern gene expression regulation. MicroRNAs (miRNAs) have emerged as another major class of gene regulators that influence gene expression post-transcriptionally, but there remains a need to assess quantitatively their global roles in gene regulation. Here, we have constructed an integrated gene regulatory network comprised of transcription factors (TFs), miRNAs, and their target genes and analyzed the effect of regulation on target mRNA expression, target protein expression, protein–protein interaction, and disease association. We found that while target genes regulated by the same TFs tend to be co-expressed, co-regulation by miRNAs does not lead to co-expression assessed at either mRNA or protein levels. Analysis of interacting protein pairs in the regulatory network revealed that compared to genes co-regulated by miRNAs, a higher fraction of genes co-regulated by TFs encode proteins in the same complex. Although these results suggest that genes co-regulated by TFs are more functionally related than those co-regulated by miRNAs, genes that share either TF or miRNA regulators are more likely to cause the same disease. Further analysis on the interplay between TFs and miRNAs suggests that TFs tend to regulate intramodule/pathway clusters, while miRNAs tend to regulate intermodule/pathway clusters. These results demonstrate that although TFs and miRNAs both regulate gene expression, they occupy distinct niches in the overall regulatory network within the cell.
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spelling pubmed-50666192017-11-01 Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs Guo, Yu Alexander, Katherine Clark, Andrew G. Grimson, Andrew Yu, Haiyuan RNA Bioinformatics Analysis of transcription regulatory networks has revealed many principal features that govern gene expression regulation. MicroRNAs (miRNAs) have emerged as another major class of gene regulators that influence gene expression post-transcriptionally, but there remains a need to assess quantitatively their global roles in gene regulation. Here, we have constructed an integrated gene regulatory network comprised of transcription factors (TFs), miRNAs, and their target genes and analyzed the effect of regulation on target mRNA expression, target protein expression, protein–protein interaction, and disease association. We found that while target genes regulated by the same TFs tend to be co-expressed, co-regulation by miRNAs does not lead to co-expression assessed at either mRNA or protein levels. Analysis of interacting protein pairs in the regulatory network revealed that compared to genes co-regulated by miRNAs, a higher fraction of genes co-regulated by TFs encode proteins in the same complex. Although these results suggest that genes co-regulated by TFs are more functionally related than those co-regulated by miRNAs, genes that share either TF or miRNA regulators are more likely to cause the same disease. Further analysis on the interplay between TFs and miRNAs suggests that TFs tend to regulate intramodule/pathway clusters, while miRNAs tend to regulate intermodule/pathway clusters. These results demonstrate that although TFs and miRNAs both regulate gene expression, they occupy distinct niches in the overall regulatory network within the cell. Cold Spring Harbor Laboratory Press 2016-11 /pmc/articles/PMC5066619/ /pubmed/27604961 http://dx.doi.org/10.1261/rna.048025.114 Text en © 2016 Guo et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Bioinformatics
Guo, Yu
Alexander, Katherine
Clark, Andrew G.
Grimson, Andrew
Yu, Haiyuan
Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs
title Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs
title_full Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs
title_fullStr Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs
title_full_unstemmed Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs
title_short Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs
title_sort integrated network analysis reveals distinct regulatory roles of transcription factors and micrornas
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066619/
https://www.ncbi.nlm.nih.gov/pubmed/27604961
http://dx.doi.org/10.1261/rna.048025.114
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