title: Dynamic regulation of microRNA expression following interferon-γ-induced gene transcription.
abstract: MicroRNAs are major players in post-transcriptional gene regulation. Even small changes in miRNA levels may have profound consequences for the expression levels of target genes. Hence, miRNAs themselves need to be tightly, albeit dynamically, regulated. Here, we investigated the dynamic behavior of miRNAs over a wide time range following stimulation of melanoma cells with interferon-γ (IFN-γ), which activates the transcription factor STAT1. By applying several bioinformatic and statistical software tools for visualization and identification of differentially expressed miRNAs derived from time-series microarray experiments, 8.9% of 1105 miRNAs appeared to be directly or indirectly regulated by STAT1. Focusing on distinct dynamic expression patterns, we found that the majority of robust miRNA expression changes occurred in the intermediate time range (24-48 h). Three miRNAs (miR-27a, miR-30a, miR-34a) had a delayed regulation occurring at 72 h while none showed significant expression changes at early time points between 30 min and 6 h. Expression patterns of individual miRNAs were altered gradually over time or abruptly increased or decreased between two time points. Furthermore, we observed coordinated dynamic transcription of most miRNA clusters while few were found to be regulated independently of their genetic cluster. Most interestingly, several "star" or passenger strand sequences were specifically regulated over time while their "guide" strands were not.
authors: Signal Transduction Laboratory, Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors: Susanne
authors: S
authors: Reinsbach
authors: Petr V
authors: PV
authors: Nazarov
authors: Demetra
authors: D
authors: Philippidou
authors: Martina
authors: M
authors: Schmitt
authors: Anke
authors: A
authors: Wienecke-Baldacchino
authors: Arnaud
authors: A
authors: Muller
authors: Laurent
authors: L
authors: Vallar
authors: Iris
authors: I
authors: Behrmann
authors: Stephanie
authors: S
authors: Kreis
mesh_terms: D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005786:Gene Expression Regulation; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation; D059467:Transcriptome
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D035683:MicroRNAs; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma