Abstract
BackgroundMicroRNAs (miRNAs) are important regulators of gene expression encoded by a variety of organisms, including viruses. Although the function of most of the viral miRNAs is currently unknown, there is evidence that both viral and host miRNAs contribute to the interactions between viruses and their hosts. miRNAs constitute a complex combinatorial network, where one miRNA may target many genes and one gene may be targeted by multiple miRNAs. In particular, viral and host miRNAs may also have mutual target genes. Based on published evidence linking viral and host miRNAs there are three modes of mutual regulation: competing, cooperating, and compensating modes.ResultsIn this paper we explore the compensating mode of mutual regulation upon Human Cytomegalovirus (HCMV) infection, when host miRNAs are down regulated and viral miRNAs compensate by mimicking their function. To achieve this, we develop a new algorithm which finds groups, called quasi-modules, of viral and host miRNAs and their mutual target genes, and use a new host miRNA expression data for HCMV-infected and uninfected cells. For two of the reported quasi-modules, supporting evidence from biological and medical literature is provided.ConclusionsThe modules found by our method may advance the understanding of the role of miRNAs in host-viral interactions, and the genes in these modules may serve as candidates for further experimental validation.
Highlights
MicroRNAs are important regulators of gene expression encoded by a variety of organisms, including viruses
Human Cytomegalovirus (HCMV) employs diverse mechanisms for the regulation of the host system in ways that are advantageous to the virus [35]
HCMV, as other members of the herpes family, encodes for miRNAs, which were shown to participate in the complex regulation of host cell metabolism and to assist in establishing latency and immune evasion [36]
Summary
MicroRNAs (miRNAs) are important regulators of gene expression encoded by a variety of organisms, including viruses. MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs (20–24 nts) that regulate gene expression by usually binding 3’ UTRs of mRNA target transcripts. They serve as major regulators of many biological processes such as development, differentiation, growth and apoptosis. These tools are noisy and predict an excess of targets for each miRNA, with a very high false-positive rate, which stands in the way of experimental wet-lab validation This limitation is due to the fact that miRNAs are very short and their interaction with target genes is not very specific. This approach may narrow the list of target genes to more reliable candidates
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