Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects

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.

Autoregulation of glypican-1 by intronic microRNA-149 fine-tunes the angiogenic response to fibroblast growth factor in human endothelial cells

“…miR-21 is encoded by an intron of TMEM49 gene) (Löffler et al, 2007). Indeed, independent expression from intronic promoters could be one of the molecular mechanisms that explains why the expression of the miRNA and the host gene does not always correlate (Lutter et al, 2010;Monteys et al, 2010). In our case, the low correlation in the expression profiles of miR-149 (both mature and primary transcripts) and its host gene in a panel of human tissues and cell lines was indicative of independent transcriptional regulation.…”

“…This host-miRNA co-expression can have a specific functional role. In fact, an intronic miRNA can support the function of its host gene by silencing genes that are functionally antagonistic to the host, or can more generally act synergistically with the host by coordinating the expression of genes with related functions (Lutter et al, 2010). Other studies also indicate that intronic miRNAs can directly participate in the regulation of the expression of their host gene [e.g.…”

“…Other studies also indicate that intronic miRNAs can directly participate in the regulation of the expression of their host gene [e.g. the regulation of EGFL7 by its intronic miRNA miR-126 (Nikolic et al, 2010), and the regulation of ARPP-21 by miR-128b (Megraw et al, 2010)], providing negative feedback regulation (Lutter et al, 2010). By contrast, there are interesting examples that indicate that intronic miRNAs can also be transcribed from their own regulatory elements (e.g.…”

Future Perspectives in Heart Pathology Diagnosis and Therapy. How We Can Use the Micro RNA?

“…[13][14][15] As known, intronic miRNA are coded within a host gene, and very often has ability to regulate the pathways similar to those of the protein encoded by that gene. 16 That's why intracellular levels of miRNAs may provide information about regulatory pathways involved in mediating the initiation of heart remodelling. And some experimental data are in the line with this idea: it's known that MiR133a can regulate the ionchannel-encoding genes HCN2 and HCN4, 11 mir-208a is encoded in the intron of the a-myosin heavy chain gene and indirectly regulates b-myosin heavy chain and connexin-40 expression; 17 and miR-499 is intronic to the myosin gene Myh7b.…”

The enemy within: intronic miR-26b represses its host gene,ctdsp2, to regulate neurogenesis

“…From one RNA transcript, two different products are generated: One is pre-miRNA cropped by Drosha during transcription, and the other one is mature host gene messenger RNA (mRNA) (Kim and Kim 2007). Since these RNAs are coexpressed both spatially and temporally, there could be a functional relationship between an intronic miRNA and its host gene (Lutter et al 2010). Indeed, there are some experimental reports about cooperation of intronic miRNAs with their host genes for cellular function.…”