DECIPHERING POST-TRANSCRIPTIONAL REGULATION MECHANISMS IN IMMUNE SYSTEM ACTIVATION

Abstract

The activation of the immune system demands rapid and tightly regulated programs of gene expression, many of which are post-transcriptionally regulated. MicroRNA-mediated silencing, RNA-binding protein (RBP) interactions, alternative splicing, and mRNA stability are all mechanisms that influence the magnitude and duration of immune responses. The interplay of these regulatory layers in the process of immune activation, however, is poorly understood. The objective of this study was to unravel the main post-transcriptional processes and pinpoint the most important regulating molecules that are engaged during the process of immunological reaction. We used both an experimental and a computational method, using RNA sequencing (RNA-seq) to study the transcriptomic changes, then quantifying their results with qPCR (quantitative polymerase chain reaction) and interpreting the data using bioinformatics to reveal the predicted targets of microRNA and their interactions with RBPs. Immune-related regulatory networks were identified by conducting a differential gene expression and pathway enrichment analysis. We found that the genes related to the inflammatory signalings and cytokine production were highly modulated, with specific miRNA expression and RBP activity profiles. Network analysis indicated the important regulatory sites of microRNAs and RBPs to immune effector gateways. Interestingly, a number of new regulatory interactions were discovered, implying co-regulation of mRNA stability and translation in response to immune activation. Finally, this paper gives a clear picture of such post-transcriptional regulation mechanisms, which mediate the immune response and sheds new lights on the intricacy of gene regulation and generates the prospective molecular targets of therapeutic intervention in immune diseases.