Genomics Inform.  2007 Sep;5(3):107-112.

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

• Piras V
• Selvarajoo K
• Fujikawa N
• Choi S
• Tomita M
• Giuliani A
• Tsuchiya M

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.

Keyword

TLR4 innate immunity; co-regulated genes; miroRNA; dynamic regulation

MeSH Terms

Animals
Binding Sites
Cytoplasm
Gene Expression*
Gene Silencing
Immunity, Innate*
Macrophages
Mice
MicroRNAs*
RNA, Messenger
Sensitivity and Specificity
Transcription Factors
MicroRNAs
RNA, Messenger
Transcription Factors