Abstract

BackgroundmicroRNAs (miRNAs) represent a class of small (typically 22 nucleotides in length) non-coding RNAs that can degrade their target mRNAs or block their translation. Recent research showed that copy number alterations of miRNAs and their target genes are highly prevalent in cancers; however, the evolutionary and biological functions of naturally existing copy number variable miRNAs (CNV-miRNAs) among individuals have not been studied extensively throughout the genome.ResultsIn this study, we comprehensively analyzed the properties of genes regulated by CNV-miRNAs, and found that CNV-miRNAs tend to target a higher average number of genes and prefer to synergistically regulate the same genes; further, the targets of CNV-miRNAs tend to have higher variability of expression within and between populations. Finally, we found the targets of CNV-miRNAs are more likely to be differentially expressed among tissues and developmental stages, and participate in a wide range of cellular responses.ConclusionsOur analyses of CNV-miRNAs provide new insights into the impact of copy number variations on miRNA-mediated post-transcriptional networks. The deeper interpretation of patterns of gene expression variation and the functional characterization of CNV-miRNAs will help to broaden the current understanding of the molecular basis of human phenotypic diversity.

Highlights

  • MicroRNAs represent a class of small non-coding RNAs that can degrade their target mRNAs or block their translation

  • Characterization of the regulation of Copy number variation (CNV)-miRNAs from the view of their target genes We first compiled the genes regulated by CNV-miRNAs using the targets from TargetScan5.1 [32], which predicts miRNA targets based on sequence complementarities, sequence context information and binding energy

  • According to the study by Marcinkowska et al [31], a total of 209 miRNAs were found to locate in the human CNV-regions

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Summary

Introduction

MicroRNAs (miRNAs) represent a class of small (typically 22 nucleotides in length) non-coding RNAs that can degrade their target mRNAs or block their translation. Recent research showed that copy number alterations of miRNAs and their target genes are highly prevalent in cancers; the evolutionary and biological functions of naturally existing copy number variable miRNAs (CNV-miRNAs) among individuals have not been studied extensively throughout the genome. Copy number alterations of miRNAs and their regulatory genes were frequently investigated in oncogenesis [28,29,30], the evolutionary and functional impact of CNV-miRNAs on the human genome has not been studied extensively. Based on the human genomic structure variations, Marcinkowska et al recently detected about 30% miRNAs located in the human CNV-regions, indicating that non-coding RNAs have potential functional variants [31]

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