Abstract
BackgroundMicro-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.ResultsFrom 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.ConclusionsLaboratory 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-976) contains supplementary material, which is available to authorized users.
Highlights
Micro-RNAs are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes
This set of n = 2984 human genes empirically shown to be regulated by Micro ribonucleic acids (miRNAs) or sufficiently credible computationally predicted to interact with miRNAs was used for an over-representation analysis (ORA [33]) with a p-value threshold of tp = 1.0 · 10−5 and Bonferroni α correction
While the analysis suggested that this regulation might be involved in any biological process, which is supported by the absence of under-represented Gene Ontology (GO) terms in the ORA, the observed significant over-representation of GO terms clearly indicates that miRNAs play distinct biological roles, which exceed a general evenly-distributed function in gene regulation
Summary
Micro-RNAs (miRNA) are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes. Pre-miRNAs are exported from the nucleus to the cytoplasm by the RNA-binding protein exportin 5 [5] There, they are cleaved to the ~22 nucleotides-long mature miRNAs by the endoribonuclease “Dicer” [6]. Research during the last decade [10,11] identified miRNAs dysregulations in several pathophysiological processes [12] such as cancer [13], cardiovascular diseases [14], viral infections [15] and pain [16] In these and further context, miRNAs have been repeatedly found to modulate a wide range of physiological functions such as cellular differentiation, proliferation and apoptosis [17]. This suggests that miRNAmediated control targets a range of typical biological processes hinting at a distinct systems-biology function of miRNAs
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