Enhanced RNAi‐1 (Eri‐1) regulates miRNA homeostasis, rRNA processing, and lymphocyte effector functions

Abstract

Helper T cell cytokine production and effector cell differentiation are influenced by endogenous RNA interference (RNAi). Northern blot analysis revealed that many miRNAs are rapidly downregulated following antigen stimulation of B and T cells. The murine orthologue of C. elegans Eri‐1 (also known as Thex1), an exonuclease that degrades short‐interfering RNA (siRNA), is upregulated in activated T cells, and cells lacking Eri‐1 exhibited increased miRNA expression and siRNA function. However, activation‐induced miRNA downregulation still occurs in the absence of Eri‐1. Eri‐1‐deficient helper T cells are biased to differentiate into Th2 effectors, and Eri‐1 deficiency in B cells leads to reduced germinal center responses. In addition to regulating RNAi, Eri‐1 catalyzes 5.8S ribosomal RNA 3′ end processing. In its absence, ribosomes are assembled with 5.8S rRNA extended by 1–2 nucleotides, and Eri‐1 can process these aberrant ribosomes to the wildtype form in vitro and in cells. Surprisingly, Eri‐1 remains associated with ribosomal subunits after 5.8S processing is complete. Further investigation is needed to clarify the relationship between the molecular functions of Eri‐1 in ribosome biogenesis and miRNA regulation, and their contribution to the defective functions of Eri‐1‐deficient lymphocytes.