Abstract
BackgroundMicroRNA-mediated control of gene expression via translational inhibition has substantial impact on cellular regulatory mechanisms. About 37% of mammalian microRNAs appear to be located within introns of protein coding genes, linking their expression to the promoter-driven regulation of the host gene. In our study we investigate this linkage towards a relationship beyond transcriptional co-regulation.ResultsUsing measures based on both annotation and experimental data, we show that intronic microRNAs tend to support their host genes by regulation of target gene expression with significantly correlated expression patterns. We used expression data of three differentiating cell types and compared gene expression profiles of host and target genes. Many microRNA target genes show expression patterns significantly correlated with the expressions of the microRNA host genes. By calculating functional similarities between host and predicted microRNA target genes based on GO annotations, we confirm that many microRNAs link host and target gene activity in an either synergistic or antagonistic manner.ConclusionsThese two regulatory effects may result from fine tuning of target gene expression functionally related to the host or knock-down of remaining opponent target gene expression. This finding allows to extend the common practice of mapping large scale gene expression data to protein associated genes with functionality of co-expressed intronic microRNAs.
Highlights
MicroRNA-mediated control of gene expression via translational inhibition has substantial impact on cellular regulatory mechanisms
Targets of expressed host genes show correlated expression patterns We studied the relationship between host and target genes in three different mouse developmental microarray datasets: embryonic stem cell development (SCD) [27], somitogenesis (SG) [28] and neurite outgrowth (NO) [29]
Since we argue that correlated expression indicates potentially common host gene functions, we initially tested for correlations between the expression patterns of known host genes
Summary
MicroRNA-mediated control of gene expression via translational inhibition has substantial impact on cellular regulatory mechanisms. About 37% of mammalian microRNAs appear to be located within introns of protein coding genes, linking their expression to the promoter-driven regulation of the host gene. About 37% of the known mammalian miRNAs are located within the introns of protein coding genes, socalled host genes [2]. This has to be appreciated as a vague estimate since the number of annotated miRNAs varies strongly from 117 for bos taurus to 695 for homo. Gene regulation mediated by miRNAs can be categorized into 'switch', 'tuning' and 'neutral' effects [14,15]. Since the neutral regulation does not have any effect on the phenotype, it will not be discussed in this work
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