Post-transcriptional regulation of immunological responses by Regnase-1-related RNases
Takuya Uehata, Osamu Takeuchi
Abstract
Regulation of messenger RNA (mRNA) decay plays a crucial role in the control of gene expression. Canonical mRNA decay pathways are initiated by deadenylation and decapping and are followed by exonucleolytic degradation. However, recent studies revealed that endoribonucleolytic cleavage also mediates mRNA decay, and both exoribonucleolytic and endoribonucleolytic decay pathways are important for the regulation of immune responses. Regnase-1 functions as an endoribonuclease to control immunity by damping mRNAs. Particularly, Regnase-1 controls cytokines and other inflammatory mediators by recognizing their mRNAs via stem-loop structures present in the 3' untranslated regions. Regnase-1 was found to be critical for human inflammatory diseases such as ulcerative colitis and idiopathic pulmonary fibrosis. Furthermore, a set of Regnase-1-related RNases contribute to immune regulation as well as antiviral host defense. In this review, we provide an overview of recent findings as to immune-related RNA-binding proteins (RBPs) with an emphasis on stem-loop-mediated mRNA decay via Regnase-1 and related RNases and discuss how the function of these RBPs is regulated and contributes to inflammatory disorders.