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Statistical Analysis of Gene Expression in Innate Immune Responses: Dynamic Interactions between MicroRNA and Signaling Molecules  

Piras, Vincent (Institute for Advanced Biosciences, Keio University)
Selvarajoo, Kumar (Institute for Advanced Biosciences, Keio University)
Fujikawa, Naoki (Institute for Advanced Biosciences, Keio University)
Choi, Sang-Dun (Department of Molecular Science and Technology, Ajou University)
Tomita, Masaru (Institute for Advanced Biosciences, Keio University)
Giuliani, Alessandro (Institute Superiore di Sanita', Environment and Health Department)
Tsuchiya, Masa (Institute for Advanced Biosciences, Keio University)
Publication Information
Genomics & Informatics / v.5, no.3, 2007 , pp. 107-112 More about this Journal
Abstract
MicroRNAs (miRNAs) are known to negatively control protein-coding genes by binding to messenger RNA (mRNA) in the cytoplasm. In innate immunity, the role of miRNA gene silencing is largely unknown. In this study, we performed microarray-based experiments using lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type, MyD88 knockout (KO), TRIF KO, and MyD88/TRIF double KO mice. We employed a statistical approach to determine the importance of the commonality and specificity of miRNA binding sites among groups of temporally co-regulated genes. We demonstrate that both commonality and specificity are irrelevant to define a priori groups of co-down regulated genes. In addition, analyzing the various experimental conditions, we suggest that miRNA regulation may not only be a late-phase process (after transcription) but can also occur even early (1h) after stimulation in knockout conditions. This further indicates the existence of dynamic interactions between miRNA and signaling molecules/transcription factor regulation; this is another proof for the need of shifting from a 'hard-wired' paradigm of gene regulation to a dynamical one in which the gene co-regulation is established on a case-by-case basis.
Keywords
TLR4 innate immunity; co-regulated genes; miroRNA; dynamic regulation;
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