TEAMwork: Interplay of Post-Transcriptional Mechanisms, Epigenetics and Metabolism in (Auto-)Immunity

Changes in transcript abundance and isoforms, mediated by epigenetic and post-transcriptional mechanisms, are a hallmark of the development, activation, and effector functions of immune cells. How epigenetic and post-transcriptional processes are orchestrated to regulate transcription and pre-mRNA processing, and their interplay with metabolism, is emerging as important for immunity. DNA and histone modifications recruit RNA-binding proteins (RBPs) to mediate co-transcriptional RNA processing at specific chromatin loci. Simultaneously, RBPs influence the deposition of epigenetic modifications by regulating the expression of chromatin-modifying enzymes and enzymes that control the amounts of metabolites. These are used as substrates by chromatin-modifying enzymes and can influence RBP activity; thus, modulation of metabolic pathways represents a mechanism to regulate the epigenetic landscape and pre-mRNA processing. A body of work identifies emerging regulatory principles that address the interplay between epigenetics and RBPs in the nucleus, and of cytoplasmic post-transcriptional mechanisms that regulate metabolism and epigenetics. In this review, we focus on the interconnections between RBP-mediated processes, chromatin modifications, and metabolic pathways, highlighting the role that such circuits have in T- and B-lymphocytes, and in autoimmunity.