Dynamic regulation of microRNA expression following interferonγ- induced gene transcription

Susanne E. Reinsbach, Petr V. Nazarov, Demetra Philippidou, Martina Schmitt, Anke Wienecke-Baldacchino, Arnaud Muller, Laurent Vallar, Iris Behrmann, Stephanie Kreis*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)

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 interferonγ (IFNγ), 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 and 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.

Original languageEnglish
Pages (from-to)978-989
Number of pages12
JournalRNA Biology
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2012

Keywords

  • Dynamic expression
  • MicroRNA
  • Time-series microarrays
  • Transcriptional regulation

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