Lessons from studying the AU-rich elements in chronic inflammation and autoimmunity

Abstract

AU-rich elements (AREs) comprise one of the most widely studied families of regulatory RNA structures met in RNAs engaged in complex immunological reactions. A multitude of genetic, molecular, holistic and functional studies have been utilized for the analyses of the AREs and their interactions to proteins that bind to them. Data stemming from these studies brought forth a world of RNA-related check-points against infection, chronic inflammation, tumor associated immunity, and autoimmunity; and the interest to capitalize the interactions of AREs for clinical management and therapy. They also provided lessons on the cellular capabilities of post-transcriptional control. Originally thought as transcript-restricted regulators of turnover and translation, ARE-binding proteins do in fact harbor great versatility and interactivity across nuclear and cytoplasmic compartments; and act as functional coordinators of immune-cellular programs. Harnessing these deterministic functions requires extensive knowledge of their synergies or antagonisms at a cell-specific level; but holds great promise since it can provide the efficacy of combinatorial therapies with single agents.

Keywords: Animal models of inflammation; Immunopathology; Innate and adaptive immunity; RNA regulation; Regulatory RNA structures.