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Understanding cooperativity of microRNAs via microRNA association networks.

Na YJ, Kim JH - BMC Genomics (2013)

Bottom Line: In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner.On the system level, we identified cooperatively regulating miRNAs in the miRNA association network.We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: MicroRNAs (miRNAs) are key components in post-transcriptional gene regulation in multicellular organisms. As they control cooperatively a large number of their target genes, they affect the complexity of gene regulation. One of the challenges to understand miRNA-mediated regulation is to identify co-regulating miRNAs that simultaneously regulate their target genes in a network perspective.

Results: We created miRNA association network by using miRNAs sharing target genes based on sequence complementarity and co-expression patterns of miRNA-target pairs. The degree of association between miRNAs can be assessed by the level of concordance between targets of miRNAs. Cooperatively regulating miRNAs have been identified by network topology-based approach. Cooperativity of miRNAs is evaluated by their shared transcription factors and functional coherence of target genes. Pathway enrichment analysis of target genes in the cooperatively regulating miRNAs revealed the mutually exclusive functional landscape of miRNA cooperativity. In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner. Sequence and structural similarity analysis within miRNA association network showed that pre-miRNA secondary structure may be involved in the expression of mature miRNA's function.

Conclusions: On the system level, we identified cooperatively regulating miRNAs in the miRNA association network. We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar. This study demonstrates the potential importance of the secondary structures of pre-miRNAs in both cooperativity and specificity of target genes.

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Overview of identifying CMMs in MRAN. (A) The conceptual diagram shows the stepwise process by which our methodology identifies cooperativity of miRNAs. The problem statement is outlined in the right column of the figure. (B) Schematic view of our approach to create miRNA association network and then to identify cooperatively regulating miRNAs in the miRNA association network.
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Figure 1: Overview of identifying CMMs in MRAN. (A) The conceptual diagram shows the stepwise process by which our methodology identifies cooperativity of miRNAs. The problem statement is outlined in the right column of the figure. (B) Schematic view of our approach to create miRNA association network and then to identify cooperatively regulating miRNAs in the miRNA association network.

Mentions: Table 1 lists the four datasets used in the present study to create MRANs following the steps illustrated in Figure 1. Table 2 shows the distribution of miRNAs and mRNAs showing inverse expression pattern in each condition. Figure 2(A) shows the global MRAN created by superimposing four conditions specific MRANs (see Figure 1) consists of 241 miRNAs and 559 connections. In MRAN, a node corresponds to each miRNA that has the significant inverse expression pattern with its targets under each experimental condition (Pearson's correlation coefficient r < 0), and edges represent target overlap score p value < 0.05. MiRNAs were clustered into distinct groups.


Understanding cooperativity of microRNAs via microRNA association networks.

Na YJ, Kim JH - BMC Genomics (2013)

Overview of identifying CMMs in MRAN. (A) The conceptual diagram shows the stepwise process by which our methodology identifies cooperativity of miRNAs. The problem statement is outlined in the right column of the figure. (B) Schematic view of our approach to create miRNA association network and then to identify cooperatively regulating miRNAs in the miRNA association network.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852507&req=5

Figure 1: Overview of identifying CMMs in MRAN. (A) The conceptual diagram shows the stepwise process by which our methodology identifies cooperativity of miRNAs. The problem statement is outlined in the right column of the figure. (B) Schematic view of our approach to create miRNA association network and then to identify cooperatively regulating miRNAs in the miRNA association network.
Mentions: Table 1 lists the four datasets used in the present study to create MRANs following the steps illustrated in Figure 1. Table 2 shows the distribution of miRNAs and mRNAs showing inverse expression pattern in each condition. Figure 2(A) shows the global MRAN created by superimposing four conditions specific MRANs (see Figure 1) consists of 241 miRNAs and 559 connections. In MRAN, a node corresponds to each miRNA that has the significant inverse expression pattern with its targets under each experimental condition (Pearson's correlation coefficient r < 0), and edges represent target overlap score p value < 0.05. MiRNAs were clustered into distinct groups.

Bottom Line: In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner.On the system level, we identified cooperatively regulating miRNAs in the miRNA association network.We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: MicroRNAs (miRNAs) are key components in post-transcriptional gene regulation in multicellular organisms. As they control cooperatively a large number of their target genes, they affect the complexity of gene regulation. One of the challenges to understand miRNA-mediated regulation is to identify co-regulating miRNAs that simultaneously regulate their target genes in a network perspective.

Results: We created miRNA association network by using miRNAs sharing target genes based on sequence complementarity and co-expression patterns of miRNA-target pairs. The degree of association between miRNAs can be assessed by the level of concordance between targets of miRNAs. Cooperatively regulating miRNAs have been identified by network topology-based approach. Cooperativity of miRNAs is evaluated by their shared transcription factors and functional coherence of target genes. Pathway enrichment analysis of target genes in the cooperatively regulating miRNAs revealed the mutually exclusive functional landscape of miRNA cooperativity. In addition, we found that one miRNA in the miRNA association network could be involved in many cooperatively regulating miRNAs in a condition-specific and combinatorial manner. Sequence and structural similarity analysis within miRNA association network showed that pre-miRNA secondary structure may be involved in the expression of mature miRNA's function.

Conclusions: On the system level, we identified cooperatively regulating miRNAs in the miRNA association network. We showed that the secondary structures of pre-miRNAs in cooperatively regulating miRNAs are highly similar. This study demonstrates the potential importance of the secondary structures of pre-miRNAs in both cooperativity and specificity of target genes.

Show MeSH