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KMID : 1132720070050030107
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Genomics & Informatics
2007 Volume.5 No. 3 p.107 ~ p.112
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Statistical Analysis of Gene Expression in Innate Immune Responses: Dynamic Interactions between MicroRNA and Signaling Molecules
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Piras Vincent
Selvarajoo Kumar
Choi Sang-Dun
Naoki Fujikawa
Masaru Tomita
Giuliani Alessandro
Masa Tsuchiya
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Abstract
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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-downregulated 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.
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KEYWORD
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TLR4 innate immunity, co-regulated genes, miroRNA, dynamic regulation
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