| Statistical Analysis of Gene Expression in Innate Immune Responses: Dynamic Interactions between MicroRNA and Signaling Molecules. |
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Vincent Piras, Kumar Selvarajoo, Naoki Fujikawa, Sangdun Choi, Masaru Tomita, Alessandro Giuliani, Masa Tsuchiya |
1Institute for Advanced Biosciences, Keio University, 14-1 Babacho, Tsuruoka, Yamagata 997-0035, Japan. tsuchiya@ttck.keio.ac.jp
2Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea.
3Istituto Superiore di Sanita', Environment and Health Department, Viale Regina Elena 299, 00161, Rome, Italy. |
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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. |
| Keywords:
TLR4 innate immunity; co-regulated genes; miroRNA; dynamic regulation |
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