Statistical Analysis of Gene Expression in Innate Immune Responses: Dynamic Interactions between MicroRNA and Signaling Molecules.
- Author:
Vincent PIRAS
1
;
Kumar SELVARAJOO
;
Naoki FUJIKAWA
;
Sangdun CHOI
;
Masaru TOMITA
;
Alessandro GIULIANI
;
Masa TSUCHIYA
Author Information
1. Institute for Advanced Biosciences, Keio University, 14-1 Babacho, Tsuruoka, Yamagata 997-0035, Japan. tsuchiya@ttck.keio.ac.jp
- Publication Type:Original Article
- Keywords:
TLR4 innate immunity;
co-regulated genes;
miroRNA;
dynamic regulation
- MeSH:
Animals;
Binding Sites;
Cytoplasm;
Gene Expression*;
Gene Silencing;
Immunity, Innate*;
Macrophages;
Mice;
MicroRNAs*;
RNA, Messenger;
Sensitivity and Specificity;
Transcription Factors
- From:Genomics & Informatics
2007;5(3):107-112
- CountryRepublic of Korea
- Language:English
-
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-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.
