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

Guo, Yu, Alexander, Katherine, Clark, Andrew G, Grimson, Andrew, Yu, Haiyuan (November 2016) Integrated network analysis reveals distinct regulatory roles of transcription factors and microRNAs. RNA: A publication of the RNA Society, 22 (11). pp. 1663-1672. ISSN 1355-8382

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Abstract

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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNA expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Alexander, Katherine
Communities:	CSHL labs > Alexander lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	November 2016
Date Deposited:	16 Jul 2024 17:44
Last Modified:	16 Jul 2024 17:44
PMCID:	PMC5066619
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41619

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