Emerging Roles of CCCH-Type Zinc Finger Proteins in Destabilizing mRNA Encoding Inflammatory Factors and Regulating Immune Responses.

Abstract

Posttranscriptional gene regulation is a rapid and effective way to mediate the expression of inflammatory genes. CCCH-type zinc finger proteins are nucleotide-binding molecules involved in RNA metabolism pathways such as RNA splicing, polyadenylation, and messenger RNA (mRNA) decay. Among these proteins, tristetraproline, Roquins, and Regnase-1/monocyte chemotactic protein-1-induced protein-1 have been recently reported to be responsible for mRNA instability. They bind to mRNAs harboring unique motifs and induce mRNA decay. In this review we summarize current progress regarding the specific characteristics of sequences and structures in the 3' untranslated regions of mRNAs that are recognized by tristetraproline, Roquins, and Regnase-1. The target mRNAs to be destabilized by those CCCH-type zinc finger proteins also are included. Notably, most target mRNAs encode cytokines and other inflammatory mediators, suggesting the immune regulation role of CCCH zinc finger proteins. Mice carrying a genetic null allele or modification of these genes display severe symptoms of autoimmune diseases. Taken together, data show that CCCH-type zinc finger proteins play a crucial role in regulating immune response by targeting multiple mRNAs, and including decay. Further understanding the functions of these proteins may provide new therapeutic targets for immune-related disorders in the future.