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What do all the (human) micro-RNAs do?

Ultsch A, Lötsch J - BMC Genomics (2014)

Bottom Line: The present analysis transferred this knowledge to a systems-biology level.A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made.The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. j.loetsch@em.uni-frankfurt.de.

ABSTRACT

Background: Micro-RNAs (miRNA) are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes. Research has identified miRNAs dysregulations in several but distinct pathophysiological processes, which hints at distinct systems-biology functions of miRNAs. The present analysis approached the role of miRNAs from a genomics perspective and assessed the biological roles of 2954 genes and 788 human miRNAs, which can be considered to interact, based on empirical evidence and computational predictions of miRNA versus gene interactions.

Results: From a genomics perspective, the biological processes in which the genes that are influenced by miRNAs are involved comprise of six major topics comprising biological regulation, cellular metabolism, information processing, development, gene expression and tissue homeostasis. The usage of this knowledge as a guidance for further research is sketched for two genetically defined functional areas: cell death and gene expression. Results suggest that the latter points to a fundamental role of miRNAs consisting of hyper-regulation of gene expression, i.e., the control of the expression of such genes which control specifically the expression of genes.

Conclusions: Laboratory research identified contributions of miRNA regulation to several distinct biological processes. The present analysis transferred this knowledge to a systems-biology level. A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made. This knowledge can be employed to guide future research concerning the biological role of miRNA (dys-) regulations. The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.

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Related in: MedlinePlus

Venn diagram [26] visualizing the sets of genes and the sizes of their intersections. The present analysis was based on the miRNAs that resulted as the union of the three sources, i.e., evidence-based miRNA interacting genes from the miRTarBase database [18] evidence-based miRNA interacting genes from the TarBase database [19] and computationally predicted miRNA regulated genes based on an analysis using the TargetScan Human [20] software (for details of the prediction method, see appendix).
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Fig1: Venn diagram [26] visualizing the sets of genes and the sizes of their intersections. The present analysis was based on the miRNAs that resulted as the union of the three sources, i.e., evidence-based miRNA interacting genes from the miRTarBase database [18] evidence-based miRNA interacting genes from the TarBase database [19] and computationally predicted miRNA regulated genes based on an analysis using the TargetScan Human [20] software (for details of the prediction method, see appendix).

Mentions: The genes likely to be regulated by miRNAs were identified by connecting several lines of evidence using publicly available computational methods, databases and data mining tools (Table 1). A first source of miRNA regulated genes consisted of empirically shown interactions of miRNA with genes. The majority of genes with empirical evidence for interaction with a miRNA was identified from miRTarBase database [18] that hosts the currently largest amount of experimentally validated miRNA versus target interactions. From this database the miRNA versus gene interactions were used for which strong experimental evidence was indicated, which in this database was defined as being provided in the form of reporter assays or western blots (file: miRTarBase_SE_WR.xls, Release 4.5 from http://mirtarbase.mbc.nctu.edu.tw/php/download.php). This gave a set of n = 360 different miRNAs acting on n = 1472 different genes. Additional miRNA regulated genes were queried from the TarBase database [19] that hosts further experimentally validated miRNA-gene interactions. In that database, experimentally validated, or supported, interactions are derived from specific, as well as high throughput experiments, such as microarrays and proteomics (for full details, see http://diana.cslab.ece.ntua.gr/?sec=home). From this database the reported direct interactions were used. This gave a set of n = 136 different miRNAs acting on n = 798 different genes. The size of unions and intersections of these gene sets are given in Figure 1.Figure 1


What do all the (human) micro-RNAs do?

Ultsch A, Lötsch J - BMC Genomics (2014)

Venn diagram [26] visualizing the sets of genes and the sizes of their intersections. The present analysis was based on the miRNAs that resulted as the union of the three sources, i.e., evidence-based miRNA interacting genes from the miRTarBase database [18] evidence-based miRNA interacting genes from the TarBase database [19] and computationally predicted miRNA regulated genes based on an analysis using the TargetScan Human [20] software (for details of the prediction method, see appendix).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4289375&req=5

Fig1: Venn diagram [26] visualizing the sets of genes and the sizes of their intersections. The present analysis was based on the miRNAs that resulted as the union of the three sources, i.e., evidence-based miRNA interacting genes from the miRTarBase database [18] evidence-based miRNA interacting genes from the TarBase database [19] and computationally predicted miRNA regulated genes based on an analysis using the TargetScan Human [20] software (for details of the prediction method, see appendix).
Mentions: The genes likely to be regulated by miRNAs were identified by connecting several lines of evidence using publicly available computational methods, databases and data mining tools (Table 1). A first source of miRNA regulated genes consisted of empirically shown interactions of miRNA with genes. The majority of genes with empirical evidence for interaction with a miRNA was identified from miRTarBase database [18] that hosts the currently largest amount of experimentally validated miRNA versus target interactions. From this database the miRNA versus gene interactions were used for which strong experimental evidence was indicated, which in this database was defined as being provided in the form of reporter assays or western blots (file: miRTarBase_SE_WR.xls, Release 4.5 from http://mirtarbase.mbc.nctu.edu.tw/php/download.php). This gave a set of n = 360 different miRNAs acting on n = 1472 different genes. Additional miRNA regulated genes were queried from the TarBase database [19] that hosts further experimentally validated miRNA-gene interactions. In that database, experimentally validated, or supported, interactions are derived from specific, as well as high throughput experiments, such as microarrays and proteomics (for full details, see http://diana.cslab.ece.ntua.gr/?sec=home). From this database the reported direct interactions were used. This gave a set of n = 136 different miRNAs acting on n = 798 different genes. The size of unions and intersections of these gene sets are given in Figure 1.Figure 1

Bottom Line: The present analysis transferred this knowledge to a systems-biology level.A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made.The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. j.loetsch@em.uni-frankfurt.de.

ABSTRACT

Background: Micro-RNAs (miRNA) are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes. Research has identified miRNAs dysregulations in several but distinct pathophysiological processes, which hints at distinct systems-biology functions of miRNAs. The present analysis approached the role of miRNAs from a genomics perspective and assessed the biological roles of 2954 genes and 788 human miRNAs, which can be considered to interact, based on empirical evidence and computational predictions of miRNA versus gene interactions.

Results: From a genomics perspective, the biological processes in which the genes that are influenced by miRNAs are involved comprise of six major topics comprising biological regulation, cellular metabolism, information processing, development, gene expression and tissue homeostasis. The usage of this knowledge as a guidance for further research is sketched for two genetically defined functional areas: cell death and gene expression. Results suggest that the latter points to a fundamental role of miRNAs consisting of hyper-regulation of gene expression, i.e., the control of the expression of such genes which control specifically the expression of genes.

Conclusions: Laboratory research identified contributions of miRNA regulation to several distinct biological processes. The present analysis transferred this knowledge to a systems-biology level. A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made. This knowledge can be employed to guide future research concerning the biological role of miRNA (dys-) regulations. The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.

Show MeSH
Related in: MedlinePlus